Obesity is common in psoriatic patients, and it has been shown to be important for many aspects of the condition. In particular, low-calorie diets can improve the symptoms and response to treatment in pustular psoriasis. The present study investigates the influence of body-weight alteration on the disease's clinical manifestations in moderate to severe psoriasis patients treated with biological drugs. Finally, the influence of a caloric restriction was assessed. This observational transversal study enrolled 33 patients attending our Severe Psoriasis Outpatient Clinic, who were treated with biological drugs. Body Mass Index (BMI) was used as a diagnostic indicator of being overweight and of obesity. Waist circumference was also measured. Body weight and Psoriasis Area Severity Index (PASI) index were measured at follow-up visits at 4 and 8 months. Nonparametric test of Mann-Whitney was used to detect the differences between patient groups. Fisher's exact test was performed to evaluate the different results depending on the therapeutic changes of BMI. There was a strong prevalence of overweight-obese individuals in the group with a mean BMI of 30.59 +/- 6.94. Waist circumference was also above normal in the majority of the patients. Obese patients had a PASI index higher than the average of the whole group (25.03 +/- 12.43), with grade III obese patients having an average PASI of 44 +/- 3.37. At the first and second follow-ups, patients who put on weight did not achieve PASI 50; patients who had a stable weight presented variable response to treatment, while patients who decreased their weight achieved PASI 90 or PASI 75 even when not responding at the first. Further studies are needed to understand if the poor response observed in heavier patients is due to biological drugs pharmacokinetics or because therapy should be BMI based rather than administered in fixed doses, posing then an ethical consideration.