Objectives <p>Emerging evidence suggests that higher physical activity and physical fitness are associated with fewer decayed teeth (DT). This study investigates whether salivary immunoglobulin A (SIgA) mediates the association between physical activity or fitness and DT, and whether dentine caries is associated with salivary and systemic immunoglobulin levels in adults.</p> Materials and methods <p>Data were derived from the 46-year follow-up of the Northern Finland Birth Cohort 1966. Participants (<i>N</i> = 1,589) underwent clinical oral examinations using ICDAS criteria. SIgA and serum immunoglobulins (IgA, IgG, IgM) were analysed from saliva and fasting blood samples using a chemiluminescence immunoassay. Physical activity was measured objectively using wrist-worn accelerometers, and physical fitness by step testing and heart rate recovery. Mediation analyses examined whether SIgA mediated associations between physical activity or fitness and DT. Associations between immunoglobulins and DT were analysed using adjusted negative binomial regression.</p> Results <p>Descriptive analyses indicated higher SIgA levels among participants with greater dentine caries burden. No significant indirect effects of physical activity or fitness on caries through SIgA were observed. In adjusted models, higher SIgA concentrations were associated with increased DT (Exp(β) = 1.282, <i>p</i> = 0.001), whereas serum IgA, IgG, and IgM were not associated with caries.</p> Conclusions <p>No evidence was found that SIgA statistically mediated the association between physical activity or fitness and dentine caries in this dataset. Higher SIgA levels are associated with greater caries burden, suggesting a reactive rather than protective role.</p> Clinical relevance <p>Salivary SIgA may reflect immune activation in response to dentine caries rather than protection against disease, highlighting the potential role of local immunity in caries progression.</p>