<p>Understanding the long-term health effects of polychlorinated biphenyl (PCB) exposure remains a critical public health concern, particularly for Indigenous populations residing near contaminated sites. This study investigates the association between serum PCB concentrations and disability among Akwesasne Mohawk adults (<i>n</i> = 109), with a specific focus on whether low-chlorinated PCB exposure increases the risk of functional impairments. Serum samples were analyzed for 101 PCB congeners, categorized into four PCB subgroups and total PCB concentrations. Disability was assessed across six domains and overall functional impairment using the World Health Organization Disability Assessment Schedule II (WHO-DAS II). Multivariable least-squares regression models were used to estimate associations between natural log-transformed serum PCB levels and disability outcomes, adjusting for age and sex. Each log-unit increase in exposure to low-chlorinated PCBs (four or fewer chlorines) was significantly associated with a 1.12-unit increase in disability related to life activities (β = 1.12, 95% CI 0.07, 2.18). No significant associations were observed for total PCBs, dioxin-like PCBs, or higher-chlorinated congeners. Our findings suggest that low-chlorinated PCB exposure is linked to increased difficulty performing life activities at home and work. Given that inhalation is a key exposure route for these volatile PCBs, our results underscore the need for further research on airborne PCB exposure and its health effects. A larger and more comprehensive investigation is necessary to validate these findings and inform public health interventions for exposed communities.</p> Graphical Abstract <p>Inhalation of low-chlorinated PCBs from legacy contamination sites is linked to functional disability in Indigenous communities.</p> <p></p>