Humans evolved in diverse and variable environments, so understanding health and disease from evolutionary perspectives must include this consideration. In our contribution, we present an overview of early Holocene human health in changing environments via a case study from archaeological sites in contemporary Ukraine. Central and eastern Europe has received little attention to date in the literature on dietary and health transitions. We thus examine demographic, palaeopathological and stable isotope data from early Holocene (Mesolithic) and Neolithic Mariupol type cemeteries from the Dnieper River region. We find that even over a few thousand years and in a small geographic region, populations had diets that varied within and between individuals and sites, with different proportions of terrestrial and aquatic resource exploitation. Human behaviour interacted with ecology to create different health outcomes, with more sedentary and fish-eating populations showing palaeopathological evidence for increased parasite load. Whether this resulted in different fitness outcomes is an open question but, although an evolutionary perspective over a long time span provides undeniably important context, we argue that we must not overlook the impact of changes on a small, proximate scale and their effects on the health of individuals. One key challenge for the future is to link proximate and evolutionary perspectives to improve our understanding of health in the past and to influence health status positively in contemporary populations.