In July 2017, her husband was diagnosed with a glioblastoma, an aggressive brain tumor.
 She issued a public statement saying that, "We as a family will face the next hurdle together.
One thing I do know is he is the toughest person I know.
He is my hero and I love him with all my heart."
 Senator McCain underwent treatment, and after December 2017 no longer went to Washington, D.C., remaining in Arizona.

The severity of her husband's illness led to the possibility that he would not be able to finish his term in office and that the Governor of Arizona would have to appoint a successor until a special election could be held.
 There is a tradition in such situations for politically involved spouses to be named as replacements, a practice known as "widow's succession".
 The possibility became an issue in the 2018 Arizona gubernatorial election, where in the Republican primary contest incumbent governor Doug Ducey was trying to fend off a challenge from former Secretary of State of Arizona Ken Bennett.
 In May 2018, some media reports stated that Ducey was planning on naming McCain if the seat became vacant.
 To this, Bennett, who was seeking to capitalize on the dissatisfaction that some conservatives in the state had long had with the long-time senator, stated, "I promise I will not appoint Cindy McCain to US Senate as Gov of AZ."
 For his part, Ducey refused to publicly speak about the possibility.

By 2018, McCain's net worth was estimated to be at least $200 million, with most of it still due to her share of Hensley & Co.  In addition the couple owned properties in Phoenix, Sedona, the San Diego area, and in Virginia, although some properties were sold off in 2017.

McCain's attitude towards the occupant of the White House took another negative turn in February 2018, following repeated public criticism by the chief executive of her husband's nay vote that had doomed the so-called "Skinny repeal" effort to dismantle Obamacare.
 McCain said: "I think the president fails to understand this, but more importantly, in my own – from my own feeling, we need more compassion, we need more empathy, we need more togetherness in terms of working together.
We don't need more bullying, and I'm tired of it."
 In July 2018 McCain issued a public statement one year after her husband's initial prognosis, saying that "Though this diagnosis has brought many challenges, our hearts are nevertheless filled with gratitude" towards caregivers, colleagues, and friends.

John McCain died at age 81 on August 25, 2018.
 She was present at, and later expressed gratitude for, the elaborate services for her husband, which involved lying in state in the rotunda at the Arizona State Capitol, a service at the North Phoenix Baptist Church, lying in state in the United States Capitol rotunda in Washington, a service at the Washington National Cathedral, and finally burial at the United States Naval Academy Cemetery.

Once it became time, McCain reportedly indicated that she was not interested in being appointed to her husband's Senate seat, as personal participation in electoral politics did not appeal to her.
 As one former aide stated, "It is a mistake to understand the McCains as a political family.
They're a military family first and a political family second."
 Nonetheless she still wielded some influence in terms of who would be picked.
 On September 4, Ducey – who had by this time easily won the Republican primary – appointed former Arizona senator Jon Kyl to the seat, in a choice that was satisfactory to all factions within the state Republican party.
 McCain referred to Kyl as "a dear friend of mine and John's.
It's a great tribute to John that he is prepared to go back into public service to help the state of Arizona."
In July 2017, her husband was diagnosed with a glioblastoma, an aggressive brain tumor.  She issued a public statement saying that, "We as a family will face the next hurdle together. One thing I do know is he is the toughest person I know. He is my hero and I love him with all my heart."  Senator McCain underwent treatment, and after December 2017 no longer went to Washington, D.C., remaining in Arizona.
The severity of her husband's illness led to the possibility that he would not be able to finish his term in office and that the Governor of Arizona would have to appoint a successor until a special election could be held.  There is a tradition in such situations for politically involved spouses to be named as replacements, a practice known as "widow's succession".  The possibility became an issue in the 2018 Arizona gubernatorial election, where in the Republican primary contest incumbent governor Doug Ducey was trying to fend off a challenge from former Secretary of State of Arizona Ken Bennett.  In May 2018, some media reports stated that Ducey was planning on naming McCain if the seat became vacant.  To this, Bennett, who was seeking to capitalize on the dissatisfaction that some conservatives in the state had long had with the long-time senator, stated, "I promise I will not appoint Cindy McCain to US Senate as Gov of AZ."  For his part, Ducey refused to publicly speak about the possibility.
By 2018, McCain's net worth was estimated to be at least $200 million, with most of it still due to her share of Hensley & Co.  In addition the couple owned properties in Phoenix, Sedona, the San Diego area, and in Virginia, although some properties were sold off in 2017.
McCain's attitude towards the occupant of the White House took another negative turn in February 2018, following repeated public criticism by the chief executive of her husband's nay vote that had doomed the so-called "Skinny repeal" effort to dismantle Obamacare.  McCain said: "I think the president fails to understand this, but more importantly, in my own – from my own feeling, we need more compassion, we need more empathy, we need more togetherness in terms of working together. We don't need more bullying, and I'm tired of it."  In July 2018 McCain issued a public statement one year after her husband's initial prognosis, saying that "Though this diagnosis has brought many challenges, our hearts are nevertheless filled with gratitude" towards caregivers, colleagues, and friends.
John McCain died at age 81 on August 25, 2018.  She was present at, and later expressed gratitude for, the elaborate services for her husband, which involved lying in state in the rotunda at the Arizona State Capitol, a service at the North Phoenix Baptist Church, lying in state in the United States Capitol rotunda in Washington, a service at the Washington National Cathedral, and finally burial at the United States Naval Academy Cemetery.
Once it became time, McCain reportedly indicated that she was not interested in being appointed to her husband's Senate seat, as personal participation in electoral politics did not appeal to her.  As one former aide stated, "It is a mistake to understand the McCains as a political family. They're a military family first and a political family second."  Nonetheless she still wielded some influence in terms of who would be picked.  On September 4, Ducey – who had by this time easily won the Republican primary – appointed former Arizona senator Jon Kyl to the seat, in a choice that was satisfactory to all factions within the state Republican party.  McCain referred to Kyl as "a dear friend of mine and John's. It's a great tribute to John that he is prepared to go back into public service to help the state of Arizona."
Cindy McCain