PURPOSE: We determined the effects of weight regain in individuals with NAFLD following a low carbohydrate diet (LC). METHODS: Twelve obese subjects (body-mass index, 36.5±1.0kg/m2) with NAFLD (10.3 ± 2.8%) followed a LC (<60g/d) energy-deficit diet (1,200kcals/day) for 12 weeks. Participants were followed-up at 9 months after the end of the weight loss (WL) phase. DXA, Magnetic resonance spectroscopy, muscle biopsies, and a euglycemic-hyperinsulinemic clamp were used to determine body composition, intrahepatic triglyceride content (IHTG), and insulin action before, after ~12 weeks of caloric restriction using a LC diet, and 9 months follow-up (post weight loss). RESULTS: Participants lost a significant (p<0.05) amount of body weight from baseline (101.9 ± 4.0kg) to 12 weeks WL (93.4 ± 4.0kg) but regained most of the body weight body at 9 months follow-up (97.5 ± 5.5kg, p>0.05 compared to baseline). IHTG significantly (p<0.05) decreased from baseline (12.4 ± 2.9%) to 12-weeks WL (8.9 ± 7.3%) but returned to baseline values at 9 months follow-up (11.5 ± 8.9%, p>0.05 compared to baseline). Basal glucose rate of appearance significantly decreased from baseline (14.2 ± 0.4 μmol/kgFFM/min, p<0.001) to WL (11.7 ± 0.3 μmol/kgFFM/min) but returned to baseline values at 9 months follow up (13.2 ± 1.5 μmol/kgFFM/min, p>0.05 compared to baseline). Homeostasis model assessment (HOMA-IR) significantly (p<0.01) decreased from baseline (4.9 ± 0.7) to WL (2.7 ± 0.5) but returned to baseline values at 9 months follow up (4.6 ± 1.6, p>0.05 compared to baseline). CONCLUSIONS: Weight regain results in the metabolic profile of obese individuals with NAFLD to return to pre-weight loss levels; emphasizing the need for effective approaches to prevent weight regain following clinically significant weight loss.