The three-times World Player of the Year picked up a fifth yellow card of the campaign at Atletico Madrid last Sunday, when his quick-thinking earned Barca a late 2-1 victory, and misses his first league game this season.
Messi is Barca's leading scorer this year with 43 goals in all competitions - he also netted a hat-tick with Argentina in a friendly on Wednesday - but his team mates will have to survive without his inspirational presence at the Nou Camp.
Pep Guardiola's side cannot afford any more slip ups as they try to keep pace with a relentless Real Madrid, who have won 19 of their last 20 league matches.
The Catalans retain slim hopes of securing a fourth consecutive league title, but trail their arch-rivals by 10 points with 14 matches left to play.
They can cut that gap to seven for 24 hours with Real not hosting Espanyol until Sunday.
Sporting are 19th and six points from safety, and have drawn their last two games since outspoken former Spain boss Javier Clemente took charge last month.
The 61-year-old, who coached Guardiola in the national team, played down comments his opposite number made last weekend after the victory at Atletico, when he said he did not think Barca would win the league.
"I know Pep quite well, and it's a phrase you come out with, but within the dressing room I am sure he will be telling his players to keep the faith," Clemente told reporters.
HOUSE HUNTING
Real receive eighth-placed Espanyol when Jose Mourinho will be the centre of attention again at the Bernabeu.
The Portuguese coach was photographed in London during the week, with media reporting he was buying a house, which prompted further speculation that he was preparing the ground for a possible exit at the end of the season.
In the battle for the other two Champions League berths, third-placed Valencia visit Granada on Sunday, and fifth-placed Athletic Bilbao are at home for the Basque derby against Real Sociedad.
There are seven teams separated by three points between fourth and tenth and one of the most interesting clashes this weekend is between Sevilla and Atletico Madrid on Saturday.
Improving Sevilla in tenth have won their last two matches under new coach Michel, while Atletico in ninth suffered their first defeat in 2012 when they lost to Barca last weekend.
Atletico will be without suspended top scorer Radamel Falcao, who has netted 15 goals this season.
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