The results of investigations performed on more than 23,500 mammoth bones and teeth in Northern Eurasia from 2003 to 2013 with the aim of revealing traces of enzootic diseases are presented here. The study focused on the Late Pleistocene “beast solonetz” sites (i.e. mineral licks/oases) of Western Siberia: Shestakovo-Kochegur (25.9–17.8 ka BP) in the Kemerovo region, Volchia Griva (17.8–11 ka BP) in the Novosibirsk region and Lugovskoye (16.5–10 ka BP) nearby Khanty-Mansiysk. Additional sites studies included sites (30–10 ka BP) from other regions of Northern Eurasia also with mass mammoth remains (Gari, Berelyokh, Krasnoyarskaya Kurya, Krakow Spadzista Street, Předmosti, Dolni Věstonice, Milovice and others). The results suggest that just at the end of the Pleistocene, large herbivorous mammals experienced a powerful geochemical stress which would manifest as mass destructive changes of bones due to enzootic diseases caused by mineral deficiency. Remains characterized by destructive changes are common and prevalent in all collections. Maximum damage was discovered in the bones and teeth of Mammuthus primigenius Blum. The most typical signs of osteodystrophy were osteoporosis, osteofibrosis, osteomalacia, osteolysis, cartilage atrophy, exostoses and fractures, resulting in the formation of false joints, ulcers and friction grooves on articular surfaces. The results of the paleoecological analysis suggest that the larger part of Northern Eurasia at the end of Pleistocene was extremely unfavourable for the existence of megafauna. The disruption of the abiotic relationships caused by the cardinal transformation of geochemical landscapes could have become the main reason for the wide-spread enzootia and, finally, the extinction of the mammoth.