In the absence of their skipper, Argentina were totally second best against Spain and shipped six goals in a 6-1 defeat - marking their heaviest defeat to European opposition since 1958.
The FC Barcelona striker will probably only play half of the game as a precaution after struggling with a groin injury which saw him sit out Argentina's 2-0 win at home against Italy. He told us before the last friendly.
"Nobody expects Portugal to win it and Messi, even before we get to talk about whether he's the greatest of all time, still has to counter the argument of whether he's as good as Maradona".
Costa was the clear favourite after starting five of Spain's opening six World Cup qualifiers but his fall-out with Chelsea, that led to five months stewing in Brazil, prompted Lopetegui into a rethink. If he is not right, he has the confidence to speak to the doctors and the necessary decision will be taken.
"We made a decision to wait for this game [against Italy] to rest, but I'm optimistic about playing against Spain".
Messi will return to training with Barca later this week, and the club expect him to be available for Saturday's trip to Sevilla.
"With me in the national team he played further out on the left, which he's not as used to". That's what I have done throughout my career. "We've just played the world champions (Germany) and now face the runners-up who have an incredible player, who collectively have improved with the arrival of Sampaoli". I feel more sluggish. The interpretation of a player with such a capacity inside the pitch gives the coach a better perspective of what is coming because his lenses are probably much more developed than ours.