LOSC currently sit third in the top-flight but that did not stop Sebastien Haller scoring the only goal of the game for the Ligue 2 outfit with seven minutes of extra-time remaining to shock Rene Girard's men.
Fellow second-tier side Troyes will join Auxerre in the fourth round as they beat Valenciennes 3-1.
VA currently sit bottom of Ligue 1 and their season went from bad to worse as Yohan Court's early strike and a brace from Ghislain Gimbert rendered Mathieu Dossevi's goal a mere consolation.
Tours are also through after beating Championnat National outfit Amiens 3-1.
Youssef Adnane and Bryan Bergougnoux put Tours two up shortly before Jonathan Tehoue was sent off for the visitors.
Despite being a man short, Amiens got back in it through a Nicolas Seguin own goal but Xavier Chavalerin sealed the win a minute from time.
Last season's beaten finalists Rennes needed extra time to get past Ligue 2 Nancy 2-1.
Adrien Hunou had Rennes ahead before half-time but Remi Walter sent the game into extra time in the final minute of the 90.
Nancy were to be left heartbroken, however, as Conceicao Emerson grabbed a winner 11 minutes into the the first extra period.
Goals from Abel Aguilar, Oscar Trejo and Wissam Ben Yedder saw Toulouse through with a 3-1 win over Cretail, for whom Nicolas Belvito scored just after the half-hour.
Alejandro Bedoya and Georges Nkoudou were on target as Nantes beat Lorient 2-0 in an all Ligue 1 clash while Araujo Ilan scored the only goal as Bastia beat Ajaccio.