Many koalas (Phascolarctos cinereus) in the Mount Lofty Ranges population, South Australia are affected by oxalate nephrosis, characterised by renal calcium oxalate deposition and kidney failure. Environmental factors such as the hot, dry summer period of the Mount Lofty region may increase the occurrence of this disease, particularly since koalas primarily rely on the moisture content of eucalypt leaves to maintain hydration. This study investigated seasonal variation in occurrence of oxalate nephrosis in koalas and whether temperature, rainfall and/or eucalypt leaf moisture were significant factors. Koalas from the Mount Lofty population that died or were euthanased between 2008 and 2016 were necropsied and oxalate nephrosis confirmed with histopathology (n = 65). Moisture content was determined in leaves from four species of dietary eucalypts collected seasonally over one year in the region. Deaths from oxalate nephrosis were significantly correlated with high mean maximal temperatures in the month of death (P < 0.05) and the month prior to death (P < 0.005), and low rainfall in the month prior to death (P < 0.05). Winter was the season when the lowest number of koalas with oxalate nephrosis were identified (P < 0.05). Average leaf moisture content was found to remain relatively constant across the year, varying from 60.3 ± 1.0% in autumn to 62.5 ± 1.0% in spring. Hence hot and dry weather was identified as an important environmental factor for increasing occurrence of death of koalas with oxalate nephrosis in the Mount Lofty region, likely due to increased evaporative water loss.