Delirium is a common complication in acute ischemic stroke, possibly caused by alterations in the regulation of the sympathetic autonomic nervous system. We investigated whether such an association could be demonstrated with two easy-to-use measurement techniques: Measurement of palmar skin conductance level (SCL) and pupillometry measuring the dilation velocity in the pupillary light reflex (PLR_dil.vel.). The cohort study included 64 patients admitted with acute ischemic stroke. During the study period (median 4.1 days, interquartile range 2.1 days) patients were assessed for delirium once daily as well as with measurements of SCL and PLR_dil.vel up to twice daily. SCL and PLR_dil.vel. during delirium were lower than without delirium present. For SCL the unadjusted difference was −40.8% (95% CI (−55.1 to −22.0), P value <.001) and for PLR_dil.vel the unadjusted difference was −0.22 mm/s (95% CI (−0.42 to −0.01), P value = .041). The results demonstrate changes in sympathetic autonomic nervous system regulation during delirium in acute stroke patients.