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Barca looked rattled for a moment but restored their lead on the half-hour when Frenkie de Jong fed compatriot Depay and the Dutch forward flummoxed visiting goalkeeper David Soria with an early strike which crept inside the near post.
Mbappé combined with Messi, but the former Barcelona striker was not in the same condition as the Frenchman, having not played a competitive game since winning the Copa America with Argentina on 10 July.
The first-half scoring was not done there as Giroud converted from the penalty spot just before the interval to make it 4-1.
Gueye is injured as well, as are right-back Colin Dagba and striker Mauro Icardi.
These facts should all be considered to place a successful bet on this match.