The influence of diet composition and availability on liver and antioxidant system function under sleep deprivation (SD) in rats is not completely known. We have previously demonstrated that chow-fed sleep-deprived rats lose weight and present a starvation-like metabolic and hormonal profile, accompanied by hyperphagia. On the other hand, liquid diet attenuates weight loss and the endocrine-metabolic effects associated to SD. It is widely known that energy metabolism is strongly correlated with the production of free radicals and that oxidative cell damage may occur. Our objective was to verify whether the two different diets offered during SD would also affect antioxidant defense system and liver integrity. Male rats were distributed into the following groups: control, sleep-deprived for 96 h by the platform technique (SD-96h) or SD-96h recovered for 24 h (Rebound). Rats were fed with chow pellets (CP) or a liquid diet (LD). Our results show that the CP rats showed changes in antioxidant defense parameters and liver damage markers after SD. However, such changes were attenuated in rats fed the liquid diet. We conclude that the attenuated effect of LD on some studied liver damage and antioxidant defense markers lead us to suggest that these changes are at least partially linked to energy deficits induced by SD.