Background: The most direct way in which climate change is expected to affect public health relates to changes in mortality rates associated with exposure to ambient temperature. Many countries worldwide experience annual heat-related and cold-related deaths associated with current weather patterns. Future changes in climate may alter such risks. Estimates of the likely future health impacts of such changes are needed to inform public health policy on climate change in the UK and elsewhere. Methods: Time-series regression analysis was used to characterise current temperature-mortality relationships by region and age group. These were then applied to the local climate and population projections to estimate temperature-related deaths for the UK by the 2020s, 2050s and 2080s. Greater variability in future temperatures as well as changes in mean levels was modelled. Results: A significantly raised risk of heat-related and cold-related mortality was observed in all regions. The elderly were most at risk. In the absence of any adaptation of the population, heat-related deaths would be expected to rise by around 257% by the 2050s from a current annual baseline of around 2000 deaths, and cold-related mortality would decline by 2% from a baseline of around 41 000 deaths. The cold burden remained higher than the heat burden in all periods. The increased number of future temperature-related deaths was partly driven by projected population growth and ageing. Conclusions: Health protection from hot weather will become increasingly necessary, and measures to reduce cold impacts will also remain important in the UK. The demographic changes expected this century mean that the health protection of the elderly will be vital.