During the sit-down, James spoke of sports as something that unites people, and added that the president was "using sports to kinda divide us".
"For someone to try to divide us by using our platform of sport?" he told Nichols.
This is not the first time James has been thrust into the political limelight for speaking out against Trump.
"Lebron James was just interviewed by the dumbest man on television, Don Lemon", Trump tweeted. He sits down with @donlemon at the opening of his new elementary school for at-risk children in his hometown of Akron, Ohio. Trump is travelling to OH on Saturday for a campaign rally. "I'd never sit across from him".
Additionally, Trump's insult has highlighted a number of comparisons between Trump's and James' accomplishments and behavior, many of which do not redound to Trump's benefit - most obviously, James' new school and Trump University.More news: Facebook Might've Just Had The Worst Day In Stock Market History
On Friday night, as James was interviewed by CNN's Don Lemon-another occasional target of Trump's-the president felt compelled to tweet something nasty.
"So let me get this straight: Flint, MI has dirty water still, but you anxious about an interview about a man doing good for education and generations of kids in his hometown?"
Other players from around the league, including Minnesota's Karl-Anthony Towns and Utah's Donovan Mitchell, came to James' defense on social media. He responded, "I don't think so", until Lemon brought up Trump as a possible opponent. "I believe there's someone else out there".
In 2013, Mr Trump tweeted: "Lebron is a great player and a great guy!"
CNN's Lemon and Don Rather have since responded to the inflammatory remarks by Trump, Rather calling the president a disgrace and Lemon questioning who the "real dummy" is.