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Background: No studies have investigated the systemic and local sinonasal profile of obesity‐related chronic rhinosinusitis (CRS), despite its observed association in recent retrospective studies. The objectives of our study were to assess the impact of obesity on the clinical and cytokine profile of patients with CRS and evaluate treatment response with functional endoscopic sinus surgery. Methods: This was a prospective observational study at the Cleveland Clinic that included patients with CRS (n = 54) between December 2021 and September 2022. Data collection included demographics, body mass index (BMI), comorbidities, baseline sinonasal outcome test scores, baseline radiologic scores (Lund–Mackay), postoperative sinonasal outcome test scores (at 3–4 months), and local and systemic alarmins/T‐helper cytokines. Results: Out of the 54 CRS patients, there were 20 CRS patients without nasal polyps (37%) and 34 with nasal polyps (63%). Patients were categorized based on obesity (BMI ≥ 30 kg/m2). Obese CRS patients had lower systemic alarmins (interleukin [IL]‐33 and Thymic stromal lymphopoietin (TSLP)) compared to non‐obese CRS patients (IL‐33: 744.2 ± 1164.6 pg/mL vs. 137.5 ± 320.0 pg/mL, p = 0.005; TSLP: 627.7 ± 1806.3 pg/mL vs. 28.1 ± 85.4 pg/mL, p = 0.017). CRS patients with nasal polyps with BMI ≥30 kg/m2 had higher postoperative sinonasal outcome test scores and lower levels of nasal eotaxin‐3 and IL‐33 compared to BMI <30 kg/m2 counterparts. Conclusions: In conclusion, patients with obese CRS and nasal polyps displayed diminished levels of intranasal alarmins and reduced intranasal eotaxin‐3. These results potentially imply the presence of a unique, obese type 2‐low CRS phenotype that warrants further exploration. [ABSTRACT FROM AUTHOR]