We quantified the severity of upper respiratory tract disease (URTD) and immunological metrics (differential white blood cell counts and bacteria-killing ability of blood plasma) in relation to climatic variables in 20 populations of Mojave desert tortoise (Gopherus agassizii). Prevalence and infection intensity of Mycoplasma agassizii, an etiological agent of URTD, have previously been quantified for these populations (Weitzman et al.). Immunological variables were reduced by principal component analyses and separated into cells involved in inflammation (PC1) and cellular functions mediated by lymphocytes and basophils (PC2). In population-level models, the mean number of lymphocytes per individual was associated with mean annual number of days below freezing. Lymphocytes were also positively associated with mean infection intensity of M. agassizii. Additionally, prevalence of URTD was closely associated with PC1 (cells associated with inflammation). This suggests that at least two immunological strategies are involved in responding to M. agassizii, one that involves primarily lymphocytes and one that involves inflammatory mechanisms. Recent studies on immunology in Testudines suggest that a large proportion of lymphocytes in this taxon are similar to B-1 lymphocytes of mammals and have phagocytic properties. Controlled experiments are needed to understand the disease mitigation of these lymphocytes in desert tortoises.