BACKGROUND: Human beings and society are experiencing substantial consequences caused by non-optimum temperatures. However, limited studies have assessed the economic burden of premature deaths attributable to non-optimum temperatures. OBJECTIVES: To characterize the association between daily mean temperature and the economic burden of premature deaths. METHODS: A total of 3 228 098 deaths were identified from a national mortality dataset in Italy during 2015 and 2019. We used the value of statistical life to quantify the economic losses of premature death. A two-stage time-series analysis was performed to evaluate the economic losses of premature deaths associated with non-optimum temperatures. Attributable burden for non-optimum temperatures compared with minimum risk temperature were estimated. Potential effect modifiers were further explored. RESULTS: From 2015 to 2019, the economic loss of premature deaths due to non-optimum temperatures was $525.52 billion (95% CI: $461.84-$580.80 billion), with the attributable fraction of 5.74% (95% CI: 5.04%-6.34%). Attributable economic burden was largely due to moderate cold temperatures ($309.54 billion, 95% CI: $249.49-$357.34 billion). A higher economic burden was observed for people above the age of 65, accounting for 75.97% ($452.42, 95%CI: $406.97-$488.76 billion) of the total economic burden. In particular, higher fractions attributable to heat temperatures were observed for provinces with the lowest level of GDP per capita but the highest level of urbanization. DISCUSSION: This study shows a considerable economic burden of premature deaths attributed to non-optimum temperatures. These figures can help inform tailored prevention to tackle the large economic burden imposed by non-optimum temperatures.