The purpose of this study was to compare biochemical and hormonal responses between mixed martial arts (MMA) competitors with minimal prefight weight loss and those undergoing rapid weight loss (RWL). Blood samples were taken from 17 MMA athletes (Mean± SD; age: 27.4 ±5.3yr; body mass: 76.2 ± 12.4kg; height: 1.71 ± 0.05m and training experience: 39.4 ± 25 months) before and after each match, according to the official events rules. The no rapid weight loss (NWL, n = 12) group weighed in on the day of the event (~30 min prior fight) and athletes declared not having used RWL strategies, while the RWL group (n = 5) weighed in 24 hr before the event and the athletes claimed to have lost 7.4 ± 1.1kg, approximately 10% of their body mass in the week preceding the event. Results showed significant (p < .05) increases following fights, regardless of group, in lactate, glucose, lactate dehydrogenase (LDH), creatinine, and cortisol for all athletes. With regard to group differences, NWL had significantly (p < .05) greater creatinine levels (Mean± SD; pre to post) (NWL= 101.6 ± 15–142.3 ± 22.9μmol/L and RWL= 68.9 ± 10.6–79.5 ± 15.9μmol/L), while RWL had higher LDH (median [interquartile range]; pre to post) (NWL= 211.5[183–236] to 231[203–258]U/L and RWL= 390[370.5–443.5] to 488[463.5–540.5]U/L) and AST (NWL= 30[22–37] to 32[22–41]U/L and 39[32.5–76.5] to 72[38.5–112.5] U/L) values (NWL versus RWL, p < .05). Post hoc analysis showed that AST significantly increased in only the RWL group, while creatinine increased in only the NWL group. The practice of rapid weight loss showed a negative impact on energy availability and increased both muscle damage markers and catabolic expression in MMA fighters.