Fast forward several hours to 3:20 a.m. Saturday, and the following tweet popped up on the @HillaryClinton twitter feed: "It's 3:20am".
In the weeks leading up to the debate, the real estate mogul had appeared uncharacteristically disciplined in his messaging and had attempted to overcome his deep unpopularity with voters of color in a number of trips to minority communities and rolled out a childcare plan, to the left of many Republicans, in an appeal to women with help from his daughter Ivanka.
"Did Crooked Hillary help disgusting (check out sex tape and past) Alicia M become a United States citizen so she could use her in the debate?"
Some Sanders supporters have taken to Twitter voicing their disagreement with the message, but Sanders' deputy communications director Mike Casca and the Clinton campaign have pointed out how the tone of Clinton's audio is not in anyway "mocking" Sanders supporters, as some have reported.
His campaign accused the media and rival Hillary Clinton of colluding to set him up for fresh condemnation, to which she retorted: "His latest Twitter meltdown is unhinged, even for him".
"[But] what we've seen from the Trump campaign and Trump's surrogates shows that they're not capable of pulling off the valid criticism", he said.
"Clinton's assault on Trump regarding his treatment of the former Miss Universe has given him the idea that he could spin this the other way by resurrecting the Monica Lewinsky scandal", said veteran GOP strategist Ron Bonjean.
"She's nasty, but I can be nastier than she ever can be", he said of Clinton in an interview with the New York Times on Friday. Trump, who used to own the Miss Universe organization, called Machado "disgusting" and a "con".
What kind of a man, Clinton asked, "stays up all night to smear a woman with lies and conspiracy theories?"
Even Trump's most vocal allies seemed at a loss for words.
"He's being Trump. I don't have any comment beyond that", said former House Speaker Newt Gingrich, a top supporter. Generally chatty and occasionally critical of Trump, Gingrich said tersely that Trump sometimes does "strange things", but that Clinton lies.
Republican presidential candidate Donald Trump signs a hat after a rally, Friday, Sept. 30, 2016, in Novi, Mich.
Clinton's campaign and joint accounts with the party began this month with $150 million in the bank, her aides say.
Trump sought to limit the damage, tweeting back that "For those few people knocking me for tweeting at three o'clock in the morning, at least you know I will be there, awake, to answer the call!"
Clinton's tweets were reminiscent of and likely a response to a flurry of tweets Trump sent out in the early hours of Friday morning that attacked both Clinton and former Miss Universe Alicia Machado. She wants him to focus on the economy instead of sex tapes.
That gave the Clinton campaign the opening it wanted, as her team circulated videos featuring Ms Machado accusing Mr Trump of destroying her self-confidence, just as many voters were starting to cast early ballots.
According to the fact-checking website Snopes, Trump's sex tape allegation appears to refer to Machado's appearance on a reality TV show in which she is shown in bed with another participant, under the covers. The images are grainy and do not include nudity, though Machado later acknowledged in the Hispanic media that she was having sex in the video.
After mocking Donald Trump's tweeting habits, Hillary Clinton made a decision to go on a little 3 a.m. Twitter tirade of her own.