Obesity is positively associated with serum thyrotropin (TSH) concentrations at the high end of the normal range. The relationship between weight loss and thyroid function is less clear and studies to date have yielded inconsistent results. Our aim was to describe changes in thyroid function in obese people in relation to durable and significant weight loss after Roux-en-Y gastric bypass (RYGB) surgery. We recorded percentage of excess weight loss (% EWL), serum TSH and free thyroxine (fT4) before and median 4.5, 15 and 24 months after RYGB in 55 euthyroid patients with morbid obesity ranging in age from 18 to 64 years in a retrospective cohort analysis in a university hospital in Greater Manchester. Mean ± standard error preoperative weight was 135.13 ± 4.23 kg and BMI 48.08 ± 1.58 kg m−2. Patients attained nadir %EWL of 68% by median 15 months after RYGB. TSH was 2.00 ± 0.14 mU L−1 at baseline and 2.02 ± 0.22 mU L−1 at 24 months after RYGB (non-significant). Baseline fT4 was 13.46 ± 0.28 pmol L−1, and increased significantly to 15.14 ± 0.55 pmol L−1 at 24 months (P < 0.004). In conclusion, we report that weight loss after RYGB was accompanied by significant increase in serum fT4 but no change in TSH concentrations. Further study to elucidate the effect of significant weight loss on the thyroid axis is required.