Mesopelagic fishes are an important element of marine food webs, a huge, still mostly untapped food resource and great contributors to the biological carbon pump, whose future under climate change scenarios is unknown. The shrinking of commercial fishes within decades has been an alarming observation, but its causes remain contended. Here, we investigate the effect of warming climate on mesopelagic fish size in the eastern Mediterranean Sea during a glacial–interglacial–glacial transition of the Middle Pleistocene (marine isotope stages 20–18; 814–712 kyr B.P.), which included a 4°C increase in global seawater temperature. Our results based on fossil otoliths show that the median size of lanternfishes, one of the most abundant groups of mesopelagic fishes in fossil and modern assemblages, declined by approximately 35% with climate warming at the community level. However, individual mesopelagic species showed different and often opposing trends in size across the studied time interval, suggesting that climate warming in the interglacial resulted in an ecological shift toward increased relative abundance of smaller sized mesopelagic fishes due to geographical and/or bathymetric distribution range shifts, and the size-dependent effects of warming.