In an effort to shame Russia for its support of Syrian President Bashar al-Assad's government and its alleged use of chemical weapons, Spicer falsely claimed that Hitler "didn't even sink to using chemical weapons" during World War II.
"You had someone who was despicable as Hitler who didn't even sink to using chemical weapons," Spicer said during the daily briefing.
"So you have to, if you are Russia, ask yourself is this a country and a regime that you want to align yourself with."
When asked by reporters to clarify his statements, Spicer said: "I think when you come to sarin gas, he was not using the gas on his own people the same way that Assad is doing...He brought them into the Holocaust centers, I understand that."
Spicer apologised for his remarks in an interview with CNN's Wolf Blitzer: "I was obviously trying to make a point about the heinous acts that Assad had made against his own people last week, using chemical weapons and gas.
"Frankly, I mistakenly made an inappropriate and insensitive reference to the Holocaust, for which there is no comparison," he said. "And for that I apologise. it was a mistake to do that."
The press secretary said he was "aware" that gas chambers were used during the holocaust and added he should have "stayed focused" on Assad.
"My goal now and then is to stay focused on Assad and I should have," he said. "I realised that I had made a mistake and I didn't want to be a distraction to the president's agenda."
Spicer is facing criticism from a number of individuals and groups for his remarks. House Minority Leader Nancy Pelosi (D-CA) called for Spicer to be fired in a statement released on Tuesday (11 April) evening.
"While Jewish families across America celebrate Passover, the chief spokesman of this White House is downplaying the horror of the Holocaust," the Democratic leader said in a statement.
"Sean Spicer must be fired, and the president must immediately disavow his spokesman's statements. Either he is speaking for the president, or the president should have known better than to hire him."
The remarks also draw the rebuke of the Anne Frank Center on Mutual Respect and others on Twitter.
"On Passover, no less, Sean Spicer has engaged in Holocaust denial, the most offensive form of fake news imaginable, by denying Hitler gassed millions of Jews to death," Steven Goldstein, the centre's executive director, said in a statement.
"Spicer's statement is the most evil slur upon a group of people we have ever heard from a White House press secretary."