Objective Cognitive impairments are a feature of bipolar disorder (BD) and could be worsened by inflammatory cytokines. We determined whether (i) serum interleukin‐1 receptor antagonist (IL‐1RA) was increased in elderly BD subjects; (ii) whether IL‐1RA was associated with worse neurocognitive function; and (iii) whether IL‐1RA was associated with white matter integrity. Methods Twenty‐one euthymic BD patients (65 +/− 9 years) with serum available for IL‐1RA measures by enzyme‐linked immunoassays were compared with 26 similarly aged control participants. Four factor analysis‐derived z‐scores and a global z‐score were obtained from a battery of 21 neurocognitive tests. Diffusion tensor images were used to obtain fractional anisotropy (FA), and an automated labeling pathway algorithm was used to obtain white matter hyperintensity burden. Results Interleukin‐1 receptor antagonist was elevated in BD subjects compared with controls (439+/−326 pg/mL vs. 269+/−109 pg/mL; p = 0.004). Moreover, IL‐1RA was inversely correlated with three cognitive function factors and global cognition (r = −0.37; p = 0.01). IL‐1RA continued to correlate with global cognitive function even when covarying for either IL‐6 or brain‐derived neurotrophic factor. Although FA was lower in BD subjects (0.368 +/− 0.02 vs. 0.381 +/− 0.01; p = 0.02), IL‐1RA was not associated with FA or white matter hyperintensity burden. Conclusion Elevated serum levels of IL‐1RA in BD subjects, even during euthymic states, were associated with worse cognitive function. This association was not explained by co‐occurring increases in IL‐6, by decreased brain‐derived neurotrophic factor, nor by measures of white matter integrity. These cross‐sectional findings support the possibility that the IL‐1 family may contribute to cognitive impairments in BD. Copyright © 2013 John Wiley & Sons, Ltd.