The Argentine winger would prefer to sit out his side's clash with Malaga in order to avoid risking a yellow card, which would rule him out of the meeting with Barcelona
The Argentina international is one booking away from a one-game ban, having picked up his fourth yellow card of the season in Sunday's 3-0 win over Levante, and he fears his passionate style of play could land him in trouble ahead of the Clasico on March 23.
"I don't know, it's difficult to choose, but I would prefer not to play," Di Maria was quoted as saying by AS.
"I always give it everything and I prefer not to risk it.
"The handball [against Levante] wasn't on purpose, but those are decisions the referees make. If I have to play in Malaga I'll be a bit inhibited."
Real Madrid currently sit top of the table with a three-point lead over second-placed Atletico, while Barcelona are four points off the pace following their shock defeat to Valladolid.