There is a relationship between obesity and cognitive functioning. Our aim was to assess weight loss influence on global cognition and executive functioning (EF) in adults with obesity under a multidisciplinary weight loss program. In this six-month longitudinal study, we assessed 81 adults (age < 50 years) with body mass index (BMI) ≥ 30. EF and global cognitive performance were evaluated with the Montreal Cognitive Assessment (MoCA), Neuropsychological Battery of Executive Functions (BANFE-2) and Trail Making Test-Part B (TMT-B). Median age was 40.0 years (IQR: 31.5–47, 61% women), and the median BMI was 41.4 (IQR: 36.7–45.9). At a six-month follow-up, the mean weight loss was 2.67% (29.6% of patients achieved ≥5% weight loss). There was an improvement in EF evaluated with BANFE (p = 0.0024) and global cognition with MoCA (p = 0.0024). Women experienced more remarkable change, especially in EF. Weight loss did not correlate with cognitive performance, except for TMT-B (r-0.258, p = 0.026). In the regression analysis, only years of education predicted the MoCA score. This study showed that patients improved cognitive performance during the follow-up; nevertheless, the magnitude of weight loss did not correlate with cognitive improvement. Future studies are warranted to demonstrate if patients achieving ≥5% weight loss can improve cognition, secondary to weight loss.