Several characteristics of Totoaba macdonaldi Perciformes: Sciaenidae, including migratory movements along temperature gradients make it vulnerable to oxidative stress. Oxidative stress can also be associated with reproduction. The objectives of the present study were to examine oxidative stress indicators in liver of totoaba throughout the seasons (spring, autumn and winter), and the associated fluctuations in superficial sea temperature (SST, °C), as well as to evaluate possible variations between sexes and reproductive maturity stages. A total of 173 liver samples from totoaba captured in the Gulf of California, Mexico, were obtained from April 2010 to February 2013. Superoxide radical production (O2•−), lipid peroxidation (TBARS) levels, and activity of antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) were quantified spectrophotometrically. Generalized linear models (GLM) were used to determine which factors contribute to explain O2•− production and TBARS levels. The significant predictive variables were the seasons, which were significant in all applied models, as well as SOD and CAT activities. In general, enzyme activity was higher in immature totoaba; this was not seasonally modified. Low temperatures in winter were associated with high O2•− production and TBARS levels, particularly in totoaba that are not yet reproductively mature. Seasonal changes in sea surface temperature did not affect the oxidative stress indicators in mature totoaba (both males and females); this suggests that mature totoaba are less sensitive to temperature changes from an oxidative stress perspective.