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Vitamin D is believed to exert an immunomodulatory effect in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and may influence the intensity of inflammatory processes. Therefore, this study aimed to assess serum vitamin D levels in relation to selected cytokines in patients with CRSwNP and without nasal polyps (CRSsNP). This prospective study included patients with clinically and radiologically confirmed diseases. In total, 39 patients were included in three phenotypic groups: CRSwNP (n = 17), CRSsNP (n = 10), and controls (n = 12). Serum concentrations of vitamin D (25(OH)D3), interleukins 4, 5, 17A, interferon-γ (IFN-γ), and immunoglobulin E were assessed preoperatively. The extent of subjective and objective mucosal disease was evaluated using endoscopic and radiological staging, based on the Lund-Kennedy and Lund-Mackay scoring systems in accordance with the Sino-Nasal Outcome Test-22 (SNOT-22), respectively. Patients with CRSwNP demonstrated higher serum IL-4 and IL-5 concentrations, consistent with a Th2-skewed inflammatory profile, whereas patients with CRSsNP showed higher IL-17A and IFN-γ levels, suggesting a mixed Th17/Th1 inflammatory pattern. IL-5 was positively associated with radiological disease severity. Serum vitamin D levels tended to be inversely associated with IL-5 concentration and disease severity; however, these associations did not reach statistical significance.: The findings of this study support differences in inflammatory profiles between CRSwNP and CRSsNP and confirm an association between IL-5 and radiological disease severity. Although lower vitamin D levels showed a trend toward greater inflammatory activity and disease severity, no statistically significant associations were demonstrated in this cohort. Further studies with larger populations are warranted to clarify the role of vitamin D in CRS endotypes.