Openness to experience has important links to cognitive processes such as creativity, and to values, such as political attitudes. The biological origins of variation in openness to experience are, however, obscure. The centrality of “aesthetic chills” to high openness suggests that sympathetic nervous system activation may play a role. Here, we tested this using the low-frequency heart rate variability power measure (LF) as biomarker of sympathetic activation, tested under baseline and stress conditions in a sample of 952 subjects, and controlling for measured confounders of age, sex, height, weight and BMI. A significant association was found between LF and openness to experience (β = 0.10, 95% CI [0.02, 0.17], p < .01). These results suggest links between openness to experience and sympathetic nervous system activity explaining, at least in part, relationships of openness to such traits as aesthetic chills.