Chicago-area Catholics are reacting to the Cardinal's letter.
"What he has to say and what he has to write about I think will affect many many many many people," said Pat Holohan.
"I would say that when there's a disagreement like this between the church and the state that it's very hard," said Marlene Robin. "I think it's very difficult."
In his letter, the Cardinal wrote:
"It is physically impossible for two men or two women to consummate a marriage, even when they share a deep friendship or love. The State has no power to create something that nature itself tells us is impossible."
The Cardinal recently made similar comments to ABC7.
"The problem is with what reason tells us, not with what the faith tells us or even what the law tells us. It goes back to what is nature telling us?" Cardinal George said on December 10.
The letter comes as state lawmakers are about to introduce a bill recognizing same-sex marriage in Illinois, a measure the state's Catholic governor supports.
"This is civil marriage we're talking about for same-sex couples," said State Senator Heather Steans. "No faith, no religion that does not want to consecrate or solemnize a union will have to do so."
"The state is the one who issues the marriage certificate, which is a legal document. And therefore, it is a matter of the state to legislate," said Anthony Martinez, executive director, The Civil Rights Agenda.
The bill, which is expected to be introduced Wednesday in Springfield, faces fierce opposition from some faith-based organizations.
"This is a very important, fundamental building block institution that we should not tamper with and not try to experiment with," said David E. Smith, Illinois Family Institute.
"I would not want to in any say the Catholic Church needs to change what their belief system is at all. And this does protect that. That's very intentional," Steans said.
The State Senate and House could vote on the measure this week or next, and if it becomes law, Illinois would become the 10th state in the nation to recognize same-sex marriage.