Cardiac patients with depression have shown altered autonomic nervous system functioning, expressed as reduced heart rate variability. This may be associated with poorer physical fitness and less physical activity among depressed patients. These relationships were explored among patients enrolled in outpatient cardiac rehabilitation. 22 depressed and 22 nondepressed patients, matched for sex and age, were assessed at enrollment. The Beck Depression Inventory and structured interviews were used to measure depression. Patients completed ambulatory monitoring of ECG (i.e., Holter) and physical activity, as well as a treadmill stress test. Depression was associated with several measures of heart rate variability. Activity and fitness were lower among the depressed patients. Although exploratory, accounting for activity and fitness attenuated the relationship between depression and heart rate variability. This suggests that altered fitness and activity may help explain altered autonomic tone that characterizes patients with cardiovascular diseases who are psychologically depressed.