"He was excited about all the junk food he could eat for the role," Cruz told host Ellen DeGeneres. "After the movie he became very healthy."
"I think to gain it was fast," she added. "But then to lose it takes a while."
Loving Pablo follows the relationship between Escobar (Bardem) and Virginia Vallejo (Cruz), a journalist who had a four-year affair with the Columbian drug lord.
"At the end of shooting, I didn't want to see him like that ever again," Cruz said of Bardem. "Especially after we shot the scene at the cathedral, which is so dark and it was so tough to do, I just wanted to run away from there."
"You separate fiction and reality as much as you can, but there is that part of you that of course is going to get affected," she added.
Cruz said Loving Pablo was her second collaboration with Bardem as a couple. The pair previously co-starred in a number of films, including Jamón Jamón and Vicky Cristina Barcelona.
Cruz had discussed her working relationship with Bardem while attending the Cannes International Film Festival in May 2018.
"The fact that [Javier and I] lean on each other and trust each other so much really helps, but this is not something that we plan on doing every two years ... just once in a while, if it feels right," she said.
Cruz and Bardem married in July 2010 and are parents to 8-year-old son Leo and 5-year-old daughter Luna. Loving Pablo opens in theaters Oct. 5.