OBJECTIVE: Depression is a risk factor for cardiovascular disease (CVD), and subgroups of people with depression may be at particularly elevated CVD risk. Lower high-frequency heart rate variability (HF HRV), which reflects diminished parasympathetic activation, is a candidate mechanism underlying the depression-CVD relationship and predicts cardiovascular events. Few studies have examined whether certain depression subgroups - such as those with co-occurring affective factors - exhibit lower HF HRV. The present study sought to assess associations between co-occurring affective factors and HF HRV in people with depression. METHODS: Utilizing baseline data from the 216 primary care patients with depression in the eIMPACT trial, we examined cross-sectional associations of depression\'s co-occurring affective factors (i.e., anxiety symptoms, hostility/anger, and trait positive affect) with HF HRV. HF HRV estimates were derived by spectral analysis from electrocardiographic data obtained during a supine rest period. RESULTS: Individual regression models adjusted for demographics and depressive symptoms revealed that anxiety symptoms (standardized regression coefficient beta = -0.24, p = .002) were negatively associated with HF HRV; however, hostility/anger (beta = 0.02, p = .78) and trait positive affect (beta = -0.05, p = .49) were not. In a model further adjusted for hypercholesterolemia, hypertension, diabetes, body mass index, current smoking, CVD prevention medication use, and antidepressant medication use, anxiety symptoms remained negatively associated with HF HRV (beta = -0.19, p = .02). CONCLUSION: Our findings suggest that, in adults with depression, those with comorbid anxiety symptoms have lower HF HRV than those without. Co-occurring anxiety may indicate a depression subgroup at elevated CVD risk on account of diminished parasympathetic activation.