Understanding the proximate mechanisms of organisms' adaptations to the environment is a classical problem in evolutionary ecology. In the context of climate change, inducing increased aridity and disruption of seasonality, it is crucial to identify the potential for species responses. Here, the physiological response to food and water limitation during seasonally dry conditions were investigated. We studied two rodent species of the genus Rhabdomys, one arid and one mesic, the ranges of which overlap in a semi-arid zone of South Africa. We measured blood concentrations of physiologically relevant metabolites in semi-arid populations of the two species at the onset and the end of the dry season. We found similar shifts in blood metabolite levels in the two species, indicating malnutrition consistent with the observed degradation of habitat quality between the start and the end of the dry season. Furthermore, regardless of season, differences between the two species in blood metabolite concentrations (amylase, sodium, potassium, bilirubin, and alkaline phosphatase) were observed, that could indicate contrasting diets and water conservation abilities. Overall, we show that, as dry conditions worsen, organisms are increasingly affected by reduced food availability, and local adaptation to arid conditions may provide the arid species with an advantage to cope with semi-arid conditions. Our study shows that even mild arid conditions could have a negative impact and questions resilience of animals to harsher arid conditions.