|“||Well, I'm alive señor. Although come to think of it, I've committed a mortal sin.||„|
|—'Mother Superior Calderón' coming to a grim realization.|
|“||Claim self defense. It always works for me.||„|
John Marston first meets Mother Superior outside Las Hermanas, while she is busy fighting off a zombie, which she ultimately kills with a repeater shot. After the zombie is dead, John and Mother Superior chat, and Mother Superior says that the other nuns are not as willing to kill and are not as resourceful as John and her, so she asks John to save them inside Las Hermanas. After John does so, John asks Mother Superior if she knows anything about the zombies, and Mother Superior says that if John can find her an undead that has recently turned, she can find out more about them.
When John brings her the zombie, Mother Superior says that she suspects that it is an evil cause, and she pours Holy Water on the undead. It shortly returns to the world of the living after being briefly bathed in a blue flame, before it returns to its growling. John notes this, to which Mother Superior replies that spiritual infections are confusing things that no one can ever understand. Mother Superior and John then chat some more and Mother Superior asks John to clear out Sepulcro, and then gives him some Holy Water. When John clears out the graveyard and returns to Mother Superior, she will state that a woman mentioned to her that the cause of all this may have been caused by Abraham Reyes, so she tells John that he should travel to Escalera if he wants to know more. They don't meet again.
- In the mission, "Get Back in That Hole, Partner", Seth Briars asks John, "Who made you Mother Nature and Mother Superior, all at the same time?"
- Mother Superior can be seen in the Red Dead Redemption storyline, as a nun collecting money for the poor in the Stranger side-mission "I Know You", and the player can kill her if desired. She can be also found in Las Hermanas in the church and may also be killed there.