The Forgetting Sarah Marshall star was performing a low-key show at the ComedySportz Theatre when he started to feel sick halfway through.
After requesting some painkillers, Brand powered through and overcame nausea to complete the 90-minute set - but he was upset at himself for the disruption, according to Britain's Daily Mirror.
He told the audience, "I have a terrible pain. I need painkillers. Sorry about this. I feel nauseous now. I feel sick.
"I'm worried this might be the early stages of a migraine. I get this light disruption thing. I think I'm such a professional showman this is beyond ridiculous stopping to take medication."
During the show, Brand, who is in the midst of a divorce from wife Katy Perry, also admitted he'd recently become "disenchanted" with fame.
He said: "I'm disenchanted and disillusioned with fame. Because it is meaningless and has no value - and I started to realise that and wanted to do something valuable and truthful.
"Because the only thing we have is each other and our connection to each other and we are constantly being distracted from that."