Introduction: Overweight and obesity are linked to increased hospitalization and mortality in COVID-19 patients. This study aimed to characterize induced immune responses and deep immune cell profiles stratified by BMI in hospitalized COVID-19 patients. Methods and results: This observational multicenter cohort pilot study included 122 adult patients with PCR-confirmed COVID-19 in Denmark, stratified by BMI (normal weight, overweight, obese). Inflammation was assessed using TruCulture® and immune cell profiles by flow cytometry with a customized antibody panel (DuraClone®). Patients with obesity had a more pro-inflammatory phenotype with increased TNF-α, IL-8, IL-17, and IL-10 levels post-T cell stimulation, and altered B cell profiles. Patients with obesity showed higher concentrations of naïve, transitional, and non-isotype switched memory B cells, and plasmablasts compared to normal weight patients and healthy controls. Conclusions: Obesity in hospitalized COVID-19 patients may correlate with elevated pro-inflammatory cytokines, anti-inflammatory IL-10, and increased B cell subset activation, highlighting the need for further studies.