© Copyright 2017 Physicians Postgraduate Press, Inc. Objective: To determine the influence of body mass index (BMI) on cognition in euthymic bipolar patients and healthy matched controls in a post hoc study of 2 cross-sectional and longitudinal exploratory studies. Method: A total sample of 121 individuals was examined, which included 52 euthymic bipolar disorder I or II patients (DSM-IV-TR criteria) and 69 healthy controls matched by age and gender, categorized in 2 subgroups in terms of body mass index (BMI-factor): normal weight (BMI: 18.5-24.9 kg/m2) versus overweight-obesity (overweight, BMI: 25.0-29.9 kg/m2; and obese, BMI ≥ 30 kg/m2). Demographic, clinical, cognitive, and psychosocial functioning data were collected from 2003 until 2011. Cognitive domains studied were executive function, attention, processing speed, verbal memory, and visual memory. Fifty-four subjects (28 bipolar and 26 healthy controls) were reevaluated after 6 years of follow-up. Results: Obesity and bipolar disorder showed a significant effect on cognition in cross-sectional and long-term MANOVA analyses (F7, 111 = 2.54, P =.018 and F19, 23 = 2.25, P =.033, respectively). In the cross-sectional linear regression model, global cognitive functioning was predicted by the interaction of BMI-factor by group (β = -0.44, SE = 0.14, P =.002), current age (β = -0.44, P <.0001), and premorbid IQ (β = 0.28, P =.0002), which explained 56% of variance (F5, 115 = 29.6, P <.0001). Change in cognitive functioning over time was predicted by the interaction of BMI-factor by group (β = -0.8, SE = 0.33, P =.022) and cognition at baseline (β = -0.46, SE = 0.15, P =.004), which explained 27.65% of variance (F6, 40 = 2.548, P =.0349). Generalized estimating equations analysis showed that interaction of group by BMI (Wald χ21 = 5.37, P =.02), age (Wald χ21 = 22.08, P <.0001), and premorbid IQ (Wald χ21 = 25.65, P <.0001) were the significant predictors. Conclusions: Obesity was significantly associated with cognitive impairment in euthymic bipolar patients, and it also appeared to affect cognition in the long term.