Hashtags like #Sniffles, #TrumpSniffles and #Trumpsniffing proliferated after the Republican sniffled repeatedly in the opening minutes of the widely watched matchup.
Comedian Stephen Colbert joked that Trump "sounded like he was fighting off a cold with cocaine."
Former Democratic National Committee chairman Howard Dean likewise tweeted: "Notice Trump sniffing all the time. Coke user?"
His tweet drew widespread ire from Trump supporters, with some calling it "shameful," while others said Dean was a "loser" and asked him to "take your foot out of your mouth."
Clinton's debate comment about her opponent's "Trumped-up trickle down" positions was immediately linked to his runny nose.
Others asked about Trump's health. "Sounds like pneumonia to me," tweeted former Democratic congressman John Dingell.
Pneumonia knocked Clinton off the campaign trail for a few days earlier this month, after Trump repeatedly raised questions about her health and stamina.
"Geezus, Trump is going to make HRC sick again!" tweeted Carla Ingraham, playing on his "Make America Great Again" slogan.
In an interview with "Fox and Friends," Trump, who throughout the debate touted his "stamina," said he didn't have a cold or allergies. "There were no sniffles," he said, blaming a faulty microphone instead.
Speaking on her campaign plane to reporters, Clinton later said: "Anybody who complains about the microphone is not having a good night."
