Sources in the Senate tell CNN they have been worried about Sen. John McCain recently, following a week when the Arizona Republican was kept from the Senate to address side effects from his brain cancer treatment.

The sources described McCain as looking 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.

One source said that McCain always used to speak up in these meetings, and that he hasn’t at all recently. The source was not commenting on McCain’s mental acuity, but on his energy level, and pointing out that his lack of participation was not normal. One well known side effect of cancer treatments is fatigue.

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.”