He even went on to say, "You had ... someone as despicable as Hitler, who didn't even sink to using chemical weapons".
Watch video of Melissa McCarthy's Sean Spicer impression when it becomes available.
"He was not using the gas on his own people the same way that Assad is doing", Spicer said.
Critics noted the remark ignored Hitler's use of gas chambers to kill Jews during the Holocaust, and Spicer apologized.
"I understand this is a holy week for the Jewish people and the Christian people and to make a gaffe and a mistake like this is inexcusable and reprehensible", he said. "I got into a topic that I shouldn't of and I screwed up". "I would ask obviously for folks' forgiveness to understand that I should not have tried to make a comparison".
At a town hall meeting in the Denver area Wednesday night, Republican Representative Mike Coffman told people that President Trump's chief spokesman needs to resign or be fired because he's not serving Trump well.
Mr Spicer faced calls to quit over his comments, which came a day after the start of Jewish holiday Passover.
Spicer shared that he had not spoken to Trump this morning, but would not comment on any possible private conversations he had with the president or other White House officials on the matter.
Sean Spicer is now being ripped apart for statements he made while comparing Syrian President Bashar al-Assad to Adolf Hitler.
Ms Pelosi, the Democrats' leader in the House of Representatives, said that Mr Spicer was "downplaying the horror of the Holocaust" and should be sacked, as did the New York-based Anne Frank Centre for Mutual Respect.
On Monday, the White House clarified remarks by Mr Spicer that the use of barrel bombs by the Assad regime might lead to further military action by the US.
This is by no means the first time Fox, a network which has been criticised for its overly favourable coverage of Mr Trump, has been associated with the Trump administration.
A day later he defended his attacks against the media, telling reporters: "I think sometimes you can disagree with facts".