The president tweeted just after midnight local time time on Wednesday: "Despite the constant negative press covfefe."
The tweet immediately went viral and became one of the president's more popular posts.
He poked fun at the typo himself, tweeting around 6am: "Who can figure out the true meaning of "covfefe" ??? Enjoy!"
Many on Twitter have supplied tongue-in-cheek meanings. One user joked that "covfefe" is already a popular name for babies in states that voted for Mr Trump.
Dozens of definitions have been submitted to the Urban Dictionary website, which crowdsources meanings for slang terms.
Silicon Valley executive Andrew Crow went as far to change his last name on Twitter to Covfefe.
Mr Trump's tweet was taken down after nearly six hours online, and the president returned to his normal Twitter routine later in the morning by criticising Democrats over the probe into Russia's meddling in the 2016 election.