Mercury (Hg) and radiocesium (137Cs) are well‐known environmental contaminants with the potential to impact the health of humans and wildlife. Snakes have several characteristics conducive to studying environmental contamination but have rarely been included in the monitoring of polluted sites. We investigated the bioaccumulation of Hg and 137Cs and associations with sublethal effects (standard metabolic rate [SMR] and hemoparasite infections) in Florida green watersnakes (Nerodia floridana). We captured 78 snakes from three former nuclear cooling reservoirs on the US Department of Energy's Savannah River Site in South Carolina (USA). For captured snakes, we (1) determined whole‐body 137Cs, (2) quantified total Hg (THg) using snake tail clips, (3) conducted hemoparasite counts, and (4) measured the SMR. We used multiple regression models to determine associations among snake body size, capture location, sex, tail THg, whole‐body 137Cs, Hepatozoon spp. prevalence and parasitemia, and SMR. Average whole‐body 137Cs (0.23 ± 0.08 Becquerels [Bq]/g; range: 0.00–1.02 Bq/g) was correlated with snake body size and differed significantly by capture site (Pond B: 0.67 ± 0.05 Bq/g; Par Pond: 0.10 ± 0.02 Bq/g; Pond 2: 0.03 ± 0.02 Bq/g). Tail THg (0.33 ± 0.03 mg/kg dry wt; range: 0.16–2.10 mg/kg) was significantly correlated with snake body size but did not differ by capture site. We found no clear relationship between SMR and contaminant burdens. However, models indicated that the prevalence of Hepatozoon spp. in snakes was inversely related to increasing whole‐body 137Cs burdens. Our results indicate the bioaccumulation of Hg and 137Cs in N. floridana and further demonstrate the utility of aquatic snakes as bioindicators. Our results also suggest a decrease in Hepatozoon spp. prevalence related to increased burdens of 137Cs. Although the results are intriguing, further research is needed to understand the dynamics between 137Cs and Hepatozoon spp. infections in semiaquatic snakes. Environ Toxicol Chem 2022;41:758–770. © 2022 SETAC