This study investigated the acute inflammatory response to a repeat-sprint training session in hypoxia. Eleven amateur team-sport athletes completed a repeat-sprint training in hypoxia (RSH) protocol (4 sets of 4x4-s running sprints) in both normoxia and normobaric hypoxia (FiO2 0.145 to simulate an altitude of 3000 m) on separate days. Participants provided venous blood samples prior to (PRE), immediately after (POST), and 3 h after (3 h) completion of the protocol, and capillary blood lactate samples were taken upon arrival, at PRE, and at POST. Distance was recorded for each sprint. Venous blood samples were analysed to determine plasma concentrations of cytokines IL-1β, IL-1ra, IL-6, IL-8, IL-10, and TNFα. There was no interaction or main effect of condition for any cytokine (p > 0.05). However, time effects indicated that IL-10 was decreased by an average of 19% across the two experimental trials at 3 h compared to POST (p = 0.04), IL-6 increased by 55% from PRE to POST (p = 0.03) then decreased by 43% from POST to 3 h (p = 0.02), and IL-8 decreased by 30% from PRE to POST (p = 0.04) and was further reduced at 3 h compared to POST (by an additional 23%; p = 0.02). A time × condition interaction (p = 0.03) indicated that lactate was higher in hypoxia. There was no interaction effect or effect of condition for sprint distance (p > 0.05). These results suggest that team-sport athletes can perform a RSH session without increasing inflammation when compared to the same training session performed in normoxia.