Barcelona were contractually bound to play Lionel Messi against Mamelodi Sundowns last week.
The La Liga champions travelled to South Africa in midweek for the friendly match which they won 3-1.
Messi was brought off the bench for the final 15 minutes, but will be rested for the final league match against Real Sociedad on Sunday.
Manager Ernesto Valverde said: "Messi has carried a load of important matches, even playing with discomfort, now we have thought to rest a little.
"In South Africa he played 15 minutes for a contractual issue, but it has helped us a lot and the idea is to rest."
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Andres Iniesta will bid farewell to Barcelona after Sunday's match.
And Valverde called on his players to give the Spaniard the perfect send-off.
"We want to finish the year well against a good team," Valverde told a press conference streamed live on Barca's official website.
"It is an important game for all blaugranas because of what Andres Iniesta means and we want to end with a victory."
Iniesta's departure will create a big hole in the LaLiga champions' side, but Valverde is confident they can cope without him.
"We won't get a replica of Andres Iniesta," he said.
"We have players like Denis Suarez, (Carles) Alena or (Philippe) Coutinho, who are similar but a little more attack-minded. All of us will have to make up for his absence together."
Barca's hopes of finishing their league campaign unbeaten blew up in smoke after suffering a 5-4 defeat at Levante in their penultimate game last week.
Despite that disappointment, Valverde has applauded his players for the season they have produced.
"I'll give the team a good grade as it has been a long and hard campaign," Valverde added. "We have had a good end of the season."
Barca are without suspended midfielder Sergi Roberto following his sending off against Real Madrid earlier this month.