Captain Messi played the full 90 minutes of Argentina's 1-0 victory over Russia on Saturday, playing a role in Sergio Aguero's late winner in Moscow.
However, the 30-year-old will not travel to Krasnodar with the rest of Jorge Sampaoli's squad, with the team's official Twitter account announcing he would return to Spain.
It was stated that Messi's departure from the Argentina camp is not related to injury.
[SELECCIÓN MAYOR] Lionel Messi fue desafectado y no estará en Krasnodar ante Nigeria. Viaja tras la victoria ante Rusia rumbo a Barcelona. pic.twitter.com/MgR6OHlvGR— Selección Argentina (@Argentina) November 11, 2017
Speaking to TyC Sports after the match, he called on his team-mates to continue working hard ahead of next year's World Cup. He said: "It's complicated, we always said that.
"The reality is that there is not much time and that's why we have to make the most of it when we're together.
"The second half was tough. They pushed up and went looking for us. We have to keep going to strengthen what we have been doing, reinforcing the system the coach wants."
Messi tops the Argentina scoring charts and he praised Aguero, who became the all-time leading goalscorer for Manchester City this month, for drawing level with Hernan Crespo in third with his 35th senior international strike.
"It's important. He came from making a record with City and now he has done it here," he added.