Introduction: Heart failure with reduced ejection fraction (HFrEF) exhibits exaggerated sympathoexcitation and altered cardiac and vascular responses to muscle metaboreflex activation (MMA). However, left ventricular (LV) responses to MMA are not well studied in patients with HFrEF. The purpose of this study was to examine LV function during MMA using cardiac magnetic resonance imaging (MRI) in patients with HFrEF. Methods: Thirteen patients with HFrEF and 18 healthy age-matched controls underwent cardiac MRI during rest and MMA. MMA protocol included 6-min of isometric handgrip exercise followed by 6-min of brachial post-exercise circulatory occlusion. LV stroke volume index (SVi), end-systolic volume index (ESVi), end-diastolic volume index (EDVi) and global longitudinal strain (GLS) were measured by 2- and 4-chamber cine images. Volumes were indexed to body surface area. Heart rate (via ECG) and brachial mean arterial pressure (MAP) were recorded. Cardiac output and total peripheral resistance (TPR) were calculated. Results: SVi decreased during MMA in HFrEF (P=0.037) but not controls (P=0.392). ESVi (P=0.007) and heart rate (P<0.001) increased during MMA in HFrEF but not controls (P≥0.170). TPR (P=0.021) and MAP (P<0.001) increased during MMA in both groups. Cardiac output (P=0.946), EDVi (P=0.177), and GLS (P=0.619) were maintained from rest to MMA in both groups. Conclusions: Despite similarly maintained cardiac output, LV strain, and increased TPR in HFrEF and control groups, SVi decreased, and heart rate increased during MMA in patients with HFrEF. These findings suggest an impaired contractility reserve in response to increased TPR during MMA in HFrEF.