A federal judge has ordered her to testify in a defamation lawsuit filed by seven of Cosby's accusers.
The couple's attorneys lost the argument that the Cosbys' private conversations were protected under marital privilege.
More than 50 women have now come forward accusing the comedian of sexual assault and/or drugging them.
Many of them appeared in the A&E documentary "Cosby - the Women Speak" - produced by ABC's Lincoln Square Productions.
"I knew I had been drugged, no doubt in my mind," accuser Beverly Johnson said.
"I was in a bed - no clothes. Cosby's in the room in a robe," accuser Charlotte Fox said.
Cosby has long denied the allegations and sat down with ABC News last May.
"I have been in this business for 52 years, and I will, I've never seen anything like this," Cosby said.
Following his arrest Wednesday, he posted on Twitter "Friends and fans, Thank you."
Friends and fans, Thank You.— Bill Cosby (@BillCosby) January 1, 2016
It received several angry responses.
Cosby's attorneys say he remains in good spirits.
"He has confidence in his legal team's ability to bring about justice for him in this case," attorney Monique Pressley said.
Camille Cosby has stood by her husband since the beginning of the allegations. He called him a kind and generous man in a statement last year.
Her deposition has been scheduled for next week.
The comedian is back in criminal court the following week.