OBJECTIVE: This study used data from the 2009–2018 National Health and Nutrition Examination Survey (NHANES) to examine the associations between obesity indicators (body mass index [BMI] and body roundness index [BRI]), the inflammatory marker white blood cell count (WBC), and asthma in women. Furthermore, it explored the potential mediating role of WBC in the relationships between BMI, BRI, and asthma. METHODS: This cross-sectional study included 3,792 eligible female participants. Logistic regression, restricted cubic spline (RCS), nonlinear curve fitting, threshold effect analysis, and mediation analysis were applied to evaluate the associations of BMI, BRI, and WBC with asthma. RESULTS: Weighted analyses showed that women with asthma had significantly higher BMI, BRI, and WBC levels compared to those without asthma (all  < 0.001). After adjusting for all potential confounders, these indicators remained significantly associated with asthma risk. Quartile-based analysis indicated that women in the highest quartile (Q4) of BMI, BRI, and WBC had a significantly higher risk of asthma. RCS and nonlinear curve fitting analyses supported nonlinear associations between these indicators and asthma, suggesting potential threshold effects. Mediation analysis demonstrated that WBC partially mediated the associations between BMI, BRI, and asthma risk. CONCLUSION: This study identified significant and nonlinear associations between BMI, BRI, WBC, and asthma risk in women. WBC was shown to play a partial mediating role in these relationships, providing new evidence for understanding the inflammatory mechanisms underlying obesity-related asthma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12890-025-03885-6.