The aim of this study was to investigate whether subcutaneous melanoma impairs intrinsic cardiac function and hypoxia tolerance in mice. Additionally it was investigated whether these changes could be prevented by voluntary running-wheel exercise. The role of different molecular pathways were also analysed. Male mice (C57Bl/6NCrl) were divided into unexercised tumor-free group, unexercised melanoma group and exercised melanoma group. Experiment lasted 2.7±0.1 weeks (determined by the tumor size) after which the heart function was measured in different oxygen levels ex vivo using Langendorff method. All the melanoma mice had lower pressure amplitude (50.3%), rate of pressure production (54.1%) and decline (52.5%) in hearts ex vivo as compared to tumor-free group. There were no functional differences between the two melanoma groups. All the groups had similar weight change, heart weights, cardiomyocyte sizes, levels of Ca²⁺-channels, energy metabolism enzyme activities, lipid peroxidation and reactive oxygen species in their cardiac tissue homogenates. However, all the melanoma mice had 7.4% lower superoxidase dismutase activity compared to the control animals, which might reduce the ability of the heart to react to changes in oxidative stress. The exercising melanoma group had 28.6% higher average heart capillary density compared to the unexercised melanoma group. Short-term wheel running did not affect the tumor growth. In conclusion, subcutaneous melanoma seems to impair intrinsic heart function even prior to cachexia and these functional alterations were not caused by any of the measured molecular markers. Short-term voluntary running-wheel exercise was insufficient to alleviate the intrinsic cardiac impairments caused by melanoma.