Abstract Purpose This study aims to evaluate the effects of a VLCKD combined with omega-3 supplementation (VLCKD diet only lasted for some weeks, and it was followed by a non-ketogenic LCD for the rest of the study period) on body composition, visceral fat, satiety hormones, inflammatory and metabolic markers. Methods It has been performed a pilot open label study lasted 90 days, in a cohort of 12 women with class I obesity aged 18 to 65 years. Data on body composition (evaluated by Dual X-Ray Absorptiometry—DXA), visceral fat, satiety hormones, inflammatory and metabolic markers were recorded. Results This study showed a body weight reduction mean difference over time of −13.7 kg and the waist circumference mean difference decrease of −13.3 cm. Also, the fat mass (FM) decreased—9.1 kg and visceral adipose tissue (VAT)— 0.41 kg. No effects on fat-free mass (FFM) have been reported. Improvements were observed in the satiety hormones, with increased ghrelin and decreased leptin, and also in the metabolic profiles. Conclusions A VLCKD combined with omega-3 supplementation appears to be an effective strategy for promoting an high loss of FM with preservation of FFM in patients with class I obesity.