BackgroundIn cats, nonthyroidal illness affects serum thyroid hormone concentrations. Serum thyroxine (T4) and triiodothyronine (T3) concentrations commonly decrease, whereas free T4 (fT4) concentrations vary unpredictably. Limited information exists regarding effects on serum thyrotropin (thyroid‐stimulating hormone [TSH]) concentrations in cats with nonthyroidal illness syndrome (NTIS).ObjectivesTo characterize alterations in thyroid function that develop in cats with NTIS and to correlate these alterations with severity and outcome of the nonthyroidal illness.AnimalsTwo hundred and twenty‐two cats with NTIS and 380 clinically normal cats of similar age and sex.MethodsProspective, cross‐sectional study. All cats had serum T4, T3, free T4, and TSH concentrations measured. Cats were grouped based on illness severity and 30‐day survival.ResultsCats with NTIS had lower serum T4 and T3 concentrations than did normal cats (P < .001). Serum fT4 and TSH concentrations did not differ between groups. Serum T4, T3, and fT4 concentrations progressively decreased with increasing disease severity (P < .001). The 56 cats that died had lower T4, T3, and TSH concentrations than did the 166 survivors, with no difference in fT4 concentration. Multivariable logistic regression modeling indicated that serum T4 and TSH concentrations both predicted survival (P < .02).Conclusions and Clinical ImportanceCats with NTIS commonly develop low serum T4, T3, and TSH concentrations, the prevalence and extent of which increases with disease severity. Clinicians should consider evaluating thyroid function in cats with severe NTIS, because doing so could help determine probability of successful treatment responses before investing considerable time, effort, and finances in addressing the underlying disease.