BACKGROUND: The present study aimed to examine the effects of spirulina supplementation on pro/antioxidant status, inflammation and skeletal muscle damage markers immediately and 24 h after exhaustive exercise in elite rugby players. METHODS: Seventeen elite male Rugby Union players were randomly assigned to a spirulina (SPI: n = 9) or placebo (PLA: n = 8) group in a double-blind design. Subjects were supplemented with Spirulina platensis (5.7 g day(-1) ) or placebo (isoproteic and caloric) for 7 weeks. At baseline and after 7 weeks of supplementation, blood samples were obtained before (T0), immediately after (T1) and 24 h after (T2) exhaustive exercise. The Yoyo Intermittent Recovery Test Level 2 was used as an exhaustive exercise to induce oxidative stress (OS), inflammation and skeletal muscle damage. The studied parameters included pro/antioxidant status markers (superoxide dismutase, glutathione peroxidase, reduced glutathione/glutathione disulphide ratio, oxidised low-density lipoprotein and F2α-isoprostanes [F2-Isop]), inflammation markers (myeloperoxidase and C-reactive protein [CRP]) and skeletal muscle damage markers (lactate dehydrogenase and creatine kinase [CK]). RESULTS: Our results showed that F2-Isop, CRP and CK levels significantly increased at T1 only in the PLA group (p < 0.05, p < 0.05 and p < 0.001, respectively) with no change in the SPI group, which reflects the effect of spirulina to prevent lipid peroxidation, inflammation and skeletal muscle damage induced by exhaustive exercise. Moreover, spirulina supplementation accelerated the return to baseline values given that F2-Isop, CRP and CK levels at T2 were significantly lower than at T0 in the SPI group (p < 0.05, p < 0.01 and p < 0.001, respectively). CONCLUSIONS: Based on the markers used in the present study, our results show that spirulina supplementation potentially prevents exercise-induced lipid peroxidation, inflammation and skeletal muscle damage, and may also accelerate the recovery of some of these markers. Based on our findings, we recommend spirulina supplementation especially for those athletes who do not achieve the recommended antioxidant dietary intake and who perform a high training load aiming to reduce the magnitude of OS, inflammation and skeletal muscle damage, which could help to reduce performance losses and accelerate recovery after training/competitions throughout the season.