An acute non-invasive reduction in preload has been shown to augment cardiac mechanics to maintain stroke volume and cardiac output. Such interventions induce concomitant changes in heart rate (HR), whereas blood volume extraction reduces preload without HR changes. Therefore, the purpose of this study was to determine whether a preload reduction in isolation resulted in augmented stroke volume achieved via enhanced cardiac mechanics. Nine healthy volunteers (4 female, age 29 ± 11 years) underwent echocardiography for the assessment of left ventricular (LV) volumes and mechanics in a supine position at baseline and end-extraction following the controlled removal of 25% of total blood volume (1062 ± 342 ml). Arterial blood pressure was monitored continuously by a pressure transducer attached to an indwelling radial artery catheter. HR and total peripheral resistance were unchanged from baseline to end extraction, but systolic blood pressure was reduced (148 to 127 mmHg). LV end diastolic volume (89 to 71 ml) and stroke volume (56 to 37 ml) were significantly reduced from baseline to end extraction; however, there was no change in LV twist, basal or apical rotation. In contrast, LV longitudinal strain (-20 to -17%) and basal circumferential strain (-22 to -19%) were significantly reduced from baseline to end extraction. In conclusion, a preload reduction during blood volume extraction does not result in compensatory changes in stroke volume or cardiac mechanics. Our data suggest that LV strain is dependent on LV filling and consequent geometry whereas LV twist could be mediated by heart rate. This article is protected by copyright. All rights reserved.