A 12th-minute goal by Philippe Coutinho was not 9enough for Barcelona, who conceded two quick second-half goals to be condemned to a shock defeat at Leganes.
Barca, who only drew at home against Girona last Sunday, are losing for the first time this season after the bottom club came from behind to pull off the sensational 2-1 victory.
Coutinho had put the visitors in front with a 20-yard volley but Nabil el Zhar and Oscar Rodriguez scored twice in the 52nd and 53rd minutes.
Barca boss Ernesto Valverde lost for just the second time in La Liga since taking charge in the summer of 2017.
Leganes had just one point from five games going into the match, but snatched a whooping 3 points from it.
Barcelona will lose their lead at the top of the La Liga table if Real Madrid avoid defeat against Sevilla later on Wednesday.
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