The 2021 Route d'Occitanie (known as the La Route d'Occitanie - La Dépêche du Midi[1] for sponsorship reasons) was a road cycling stage race that took place between 10 and 13 June 2021 in the southern French region of Occitanie.

The race was the 45th edition of the Route d'Occitanie and was rated as a category 2.1 event on the 2021 UCI Europe Tour.

[1] Eight of the nineteen UCI WorldTeams, eight UCI ProTeams, three UCI Continental teams, and the French national team made up the twenty-teams that participated in the race.

Only three teams did not enter a full squad of seven riders: Ineos Grenadiers and Trek–Segafredo entered five riders each, while Cofidis entered six riders.

Of the 135 riders who started the race, 107 finished.