Data from real-world studies and clinical trials have documented the long-term efficacy and safety of guselkumab in patients with moderate-to-severe psoriasis. Limited data are available on the long-term use of guselkumab in morbidly obese individuals with severe psoriasis. Here, we present data on the outcome of three patients with class III obesity (body mass index (BMI) of ≥40 kg/m) with severe plaque psoriasis treated with 100 mg guselkumab. At baseline, mean BMI was 46.5 ± 5.4 kg/m and mean PASI was 46.0 ± 18.5 and all patients were biologic naïve. After 12 weeks of guselkumab treatment, mean PASI decreased to 9.7 ± 4 and to 4.0 ± 1.7 at 28 weeks. After 1 year, two patients achieved complete remission and one patient had PASI of 6 (achieving remission by week 140). All three patients are still in complete remission. Our real-life results in specific patients burdened with class III obesity naïve to biologic treatment show excellent long-term psoriasis outcome with guselkumab.