INTRODUCTIONVitamin D supplementation has shown promise in averting asthma. However, the association between 25(OH)D levels and asthma prevention in various demographic groups remains inconclusive. Here, we explore this relationship in the context of overweight and obese individuals in the United States.METHODSWe scrutinized cross-sectional data derived from the National Health and Nutrition Examination Survey conducted between 2007 and 2018. This dataset encompasses comprehensive information about asthma patients with a body mass index greater than 25 kg/m2, in addition to data regarding 25(OH)D concentration and other pertinent variables. Among the 3889 participants, 16.2% (631/3889) reported a history of asthma, constituting 1765 (45.4%) males and 2124 (54.6%) females. The median age was 56.0 years, with a standard deviation of 16.0 years. We conducted restricted cubic spline (RCS) regression analysis to assess the correlation between 25(OH)D levels and asthma.RESULTSAfter adjusting for confounders, compared to individuals with lower 25-hydroxyvitamin D concentration (group1 ≤ 46.6 nmol/L), the adjusted odds ratios (OR) for asthma in group2 (46.7-62 nmol/L), group3 (62.1-78.2 nmol/L), and group4 (≥78.3 nmol/L) were 0.68 (95% CI: 0.49-0.94, p < 0.021), 0.65 (95% CI: 0.47-0.88, p < 0.006), and 0.83 (95% CI: 0.61-1.12, p < 0.22), respectively. Restricted cubic spline (RCS) regression analysis revealed a nonlinear U-shaped curve (p = 0.017) with an inflection point at approximately 84.95 nmol/L.CONCLUSIONSHigh levels of 25(OH)D are correlated with a diminished prevalence of asthma among overweight and obese individuals in the United States.