Finally, four minutes before half-time, Ousmane Dembele conceded possession and Markel Susaeta's cross was perfectly weighted to evade the scrambling Sergi Roberto at the back post, where De Marcos slid the ball home.
It's the first time in two years Barcelona hasn't won in three consecutive league matches.
The France worldwide is not in contention for the Camp Nou clash against Valverde's former club and, although already suspended, would not have been fit enough for the midweek Champions League match versus Tottenham at Wembley.
"It's been a hard week, having won only one point in nine possible", Barcelona coach Ernesto Valverde said.
The Argentinean then flashed a shot off the outside of the post with 15 minutes remaining before setting up Munir, who had just come into the game as a substitute for the equalizing goal after Unai had saved his original shot. Ter Stegen had to push Raul Garcia's effort over and was then rounded by Williams but the angle proved too tight. Messi shot twice, the first scrambled away by Simon but the second fizzed across the face of goal for Munir to divert in.
The Argentine started the game from the bench and was introduced in the second half as the hosts chased an equalier.
"We have the squad and the players to be a great team, to be a strong team and not depend on anyone".
Barca have taken two points from the last three games.
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.
The size of the roar gave an indication of the approval for the decision as Messi replaced Arturo Vidal, one of several close season signings who has so far failed to spark so far for their new club.
Manager Ernesto Valverde did not bring Messi on at half time, but, with his side down against his former club, on 54 minutes, the substitute's board with was raised in the sunshine.
Even with Messi now on the pitch Barca huffed and puffed but could not find a way through.