Autonomic dysregulation may lead to blunted sympathetic reactivity in chronic pain states and autonomic responses are controlled by the central autonomic network (CAN). Little research has examined sympathetic reactivity and associations with brain CAN structures in the presence of chronic pain; thus, the present study aims to investigate chronic pain differences in sympathetic reactivity and associations with CAN brain region volumes. Sympathetic reactivity was measured as change in skin conductance level (ΔSCL) between a resting preparation and walking phases of typical and complex walking tasks (obstacle and dual-task) in 31 participants with (n=19) and without (n=12) chronic musculoskeletal pain using a repeated measures-ANCOVA with Bonferroni corrections. Structural 3T MRI was used to determine gray matter volume associations with ΔSCL in regions of the CAN (i.e., brainstem, amygdala, insula, and anterior cingulate cortex, using partial correlations (FDR-corrected) adjusting for important covariates. ΔSCL varied across all walking tasks (main effect p=0.036), with lower ΔSCL in chronic pain participants (21.0±5.4µS) compared to controls (43.4±7.5µS). ΔSCL during typical walking was associated with multiple CAN gray matter volumes, including brainstem, bilateral insula, amygdala, right caudal anterior cingulate cortex (FDRp's<0.05). ΔSCL from typical-to-obstacle walking were associated with volumes of the midbrain segment of the brainstem and anterior segment of the circular sulcus of the insula (FDRp's<0.05), with no other significant associations. ΔSCL from typical-to-dual task walking was associated with the bilateral caudal anterior cingulate cortex, and left rostral cingulate cortex (FDRp's<0.05). Sympathetic reactivity is blunted during typical and complex walking tasks in persons with chronic pain. Additionally, blunted sympathetic reactivity is associated with CAN brain structure, in a brain region-dependent manner. These results support the idea that chronic pain may negatively impact typical autonomic responses needed for walking performance via its potential impact on the brain. R01AR071431, K01AG048259, and 1 F31 AR077996-01. Autonomic dysregulation may lead to blunted sympathetic reactivity in chronic pain states and autonomic responses are controlled by the central autonomic network (CAN). Little research has examined sympathetic reactivity and associations with brain CAN structures in the presence of chronic pain; thus, the present study aims to investigate chronic pain differences in sympathetic reactivity and associations with CAN brain region volumes. Sympathetic reactivity was measured as change in skin conductance level (ΔSCL) between a resting preparation and walking phases of typical and complex walking tasks (obstacle and dual-task) in 31 participants with (n=19) and without (n=12) chronic musculoskeletal pain using a repeated measures-ANCOVA with Bonferroni corrections. Structural 3T MRI was used to determine gray matter volume associations with ΔSCL in regions of the CAN (i.e., brainstem, amygdala, insula, and anterior cingulate cortex, using partial correlations (FDR-corrected) adjusting for important covariates. ΔSCL varied across all walking tasks (main effect p=0.036), with lower ΔSCL in chronic pain participants (21.0±5.4µS) compared to controls (43.4±7.5µS). ΔSCL during typical walking was associated with multiple CAN gray matter volumes, including brainstem, bilateral insula, amygdala, right caudal anterior cingulate cortex (FDRp's<0.05). ΔSCL from typical-to-obstacle walking were associated with volumes of the midbrain segment of the brainstem and anterior segment of the circular sulcus of the insula (FDRp's<0.05), with no other significant associations. ΔSCL from typical-to-dual task walking was associated with the bilateral caudal anterior cingulate cortex, and left rostral cingulate cortex (FDRp's<0.05). Sympathetic reactivity is blunted during typical and complex walking tasks in persons with chronic pain. Additionally, blunted sympathetic reactivity is associated with CAN brain structure, in a brain region-dependent manner. These results support the idea that chronic pain may negatively impact typical autonomic responses needed for walking performance via its potential impact on the brain. R01AR071431, K01AG048259, and 1 F31 AR077996-01.