Animals in arid environments must maintain water balance despite persistent drought, heat, and low food availability. Blood serum osmolality offers an integrative physiological measure of hydration, yet no prior study has examined it in wild mammals across multiple seasons and years. Using 12 years of field data from African striped mice (Rhabdomys pumilio) inhabiting the Succulent Karoo semi-desert, we investigated seasonal variation in serum osmolality. This region features cold, moist winters with high food availability and hot, dry summers with scarce resources. Season, maximum temperature, and food availability were collinear and tested independently—each was statistically significant. Serum osmolality was higher during the dry season, particularly when food availability was low. While temperature best predicted osmolality across seasons, food availability explained more variation within the dry season. Our findings establish serum osmolality as an indicator of environmental harshness in xeric mammals.