BACKGROUND: Currently, no test can accurately predict the development of azotemia after treatment of hyperthyroidism. Serum cystatin C concentrations (sCysC) might be less influenced by changes in body muscle mass and so better indicate the presence of concurrent chronic kidney disease (CKD) in hyperthyroidism. HYPOTHESES: sCysC will be higher in hyperthyroid cats that develop azotemia compared with hyperthyroid cats that remain nonazotemic after treatment; sCysC will be higher in nonhyperthyroid cats with azotemic CKD than healthy older cats and, sCysC will decrease after treatment of hyperthyroidism. ANIMALS: Ninety-one cats treated in first opinion practice. METHODS: Case-control study. sCysC were compared between hyperthyroid cats which developed azotemia within 4 months of successful treatment of hyperthyroidism (pre-azotemic group) and hyperthyroid cats which remained nonazotemic after treatment (nonazotemic group), and between nonhyperthyroid cats with azotemic CKD and healthy older cats. sCysC were also compared between hyperthyroid cats before treatment and at time of establishment of euthyroidism. Data are presented as median [25th, 75th percentile]. RESULTS: Baseline sCysC were not different between the pre-azotemic and nonazotemic groups (1.9 [1.4, 2.3] mg/L versus 1.5 [1.1, 2.2] mg/L, respectively; P = .22). sCysC in nonhyperthyroid cats with azotemic CKD and healthy older cats were not significantly different (1.5 [1.0, 1.9] mg/L versus 1.2 [0.8, 1.4] mg/L, respectively; P = .16). sCysC did not change significantly after treatment of hyperthyroidism (pretreatment 1.8 [1.2, 2.3] mg/L, after treatment 1.6 [1.1, 2.4] mg/L; P = .82). CONCLUSIONS AND CLINICAL IMPORTANCE: sCysC do not appear to be a reliable marker of renal function in hyperthyroid cats.