Barca boss Ernesto Valverde reacted to his side's shock 2-1 midweek defeat at Leganes by resting both Sergio Busquets and star man Messi, with one eye on their upcoming match with Tottenham.
De Marcos's volley was the eighth goal the La Liga champions have conceded in seven games this season and Messi said his side urgently needed to improve in defence.
"When I make the decision, I think about what's best for my team and for my club", Valverde was quoted as saying by FootballEspana.
Messi came on in the second half and grabbed the assist for Munir El Haddadi's equaliser at the Camp Nou.
They could have doubled their lead shortly after Messi went close, but Nelson Semedo's last ditch tackle stopped Inaki Williams when he was through on goal.
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It's the first time in two years Barcelona hasn't won in three consecutive league matches.
Far from their best in terms of quality of football, in the fluidity of their offensive play, the capacity to create chances and above all, in defensive solidity.
Luis Suarez warned his Barcelona team-mates they can not afford to keep relying on Lionel Messi to solve everything after a 1-1 draw at home to Athletic Bilbao on Saturday.
Sevilla were relentless throughout the first half and after Franco Vazquez hit the bar, striker Wissam Ben Yedder scored in the 39th minute for his sixth goal in a week to stun Real, who suffered their first loss under manager Julen Lopetegu.
'We know we have to be stronger defensively, ' he said after Barcelona failed to win for the third match running. "It's an experience we've got to enjoy", he said.