ABSTRACT: BACKGROUND:Heart rate variability (HRV) and baroreflex sensitivity (BRS) measurements provide means for the objective assessment of cardiovascular autonomic function. As previous studies have associated chronic pain with abnormal autonomic function, we aimed to characterize the relationship between the number of musculoskeletal pain sites (NPS), pain intensity, and cardiovascular autonomic function among the population-based Northern Finland Birth Cohort 1966. METHODS:At the age of 46, cohort members self-reported their musculoskeletal pains (enabling the determination of NPS [0-8] and pain intensity [Numerical Rating Scale, NRS, 0-10]) and underwent clinical assessments of cardiovascular autonomic function in seated and standing positions (HRV variables: heart rate [HR] and root mean square of successive differences in beat-to-beat intervals [rMSSD] for the entire cohort; BRS variables: low-frequency systolic blood pressure variability [SBPV] and cross-spectral baroreflex sensitivity [BRS] for those attending the examination in Oulu, Finland). Extensive confounder data were also collected (body mass index, physical activity, smoking, Hopkins Symptom Checklist-25, comorbidities, and medications). The full samples included 4186 and 2031 individuals (HRV and BRS samples, respectively). Three subanalyses focused on individuals with intense and frequent pain, individuals with symptoms of depression and anxiety, and the relationship between pain intensity and autonomic parameters. RESULTS:Linear regression models showed varying associations between NPS, pain intensity, and cardiovascular autonomic parameters. However, after all adjustments NPS was only associated with one outcome among women (BRS, standing: beta?=?-?0.015, p =?0.048) and two among men (HR, seated: beta?=?-?0.902, p =?0.003; HR, standing: beta?=?-?0.843, p =?0.014). Pain intensity was not associated with any outcome after full adjustments. Significant sex*pain interactions were found in the data. CONCLUSIONS:Our data suggest that musculoskeletal pain has, at most, a limited independent association with cardiovascular autonomic function. Future studies should carefully account for the potential confounders and sex interactions that this study revealed.