The sources said the 81-year-old looked increasingly frail and said he has not spoken up in recent GOP meetings the way he had before, in addition to his absence this week for treatment at Walter Reed Medical Center.
The source noted that McCain's energy level was not as high as it previously was and that his lack of participation was not normal.
Sen. Lindsey Graham of South Carolina, McCain's closest friend in the Senate, said he spoke with Cindy McCain on Wednesday about her husband's health.
"He is receiving treatment for the side effects of therapy," Graham said. "I feel pretty good about the way the treatment is affecting his underlying cancer. But the treatment has a downside. So he is trying to rest up. I am very confident that he will come back and continue to participate for a long time to come."
Graham said he hopes to talk to McCain on Thursday or see him in person soon.
"The main thing I am focused on is to just get better. John, take a little time. Rest up. It's OK," Graham said. "Take a day or two off. He's had a heck of a Senate schedule. And I hope he will take some time to regroup, do a little rehabilitation on his leg, and come back and participate in a way that only Sen. McCain can participate."
McCain is five months into treatment for brain cancer. He was diagnosed with glioblastoma, a type of brain tumor, in July.
Arizona Sen. Jeff Flake said he also spoke with Cindy McCain on Wednesday night about her husband's health.
"We expect him back," Flake told reporters. "I expect him back. He's obviously recovering from the effects of the treatment and so we expect him back."
McCain and Biden held hands and both started tearing up when the former vice president talked about the hope that his son kept alive even after getting "this devastating diagnosis, like your dad."
"There are breakthroughs that are occurring now, and it can happen tomorrow," Biden said.
"So there is hope. And if anybody can make it, your dad [can]," he continued to applause from the audience. "Her dad is one of my best friends."0comments
Biden told McCain that her father is seeing one of the doctors his son consulted after being diagnosed with glioblastoma and that breakthroughs in glioblastoma cancer research are close.
"I swear, guys, we are going to beat this damned disease. We really are," he said.