Hypertension is characterised by both enlarged perivascular spaces (ePVS) and chronically elevated resting sympathetic outflow. ePVS is associated with heart rate variability, suggesting links to autonomic outflow; however, heart rate variability offers limited information on sympathetic nerve activity. Here, we assessed whether ePVS are associated with muscle sympathetic nerve activity (MSNA) in 25 hypertensive patients and 50 healthy normotensive adults. T1-weighted MRI anatomical brain images were analysed for ePVS using a deep learning-based segmentation algorithm (nnU-Net). Spontaneous bursts of MSNA were recorded from the right common peroneal nerve via a tungsten microelectrode immediately before the MRI scan in a supine position. A backward regression analysis was conducted to test the relationship between ePVS and MSNA. Significant associations were found between MSNA and ePVS in the white matter (β = 1.02, p = 0.007), basal ganglia (β = 0.43, p = 0.001), and hippocampus (β = 0.24, p = 0.010) in healthy normotensive adults. Similar associations were observed in individuals with hypertension. Notably, the association between MSNA and midbrain ePVS cluster was only observed in the hypertensive group (β = 0.41, p = 0.005). ePVS were associated with MSNA in both normotensive and hypertensive patients. These findings warrant further research into the causal relationship between MSNA and ePVS and highlight the potential for ePVS as a neuroimaging biomarker for sympathetic nerve activity.