Abstract Background Although adaptation to continuously rising ambient temperatures is an emerging topic and has been widely studied at a global scale, detailed analysis of the joint indicators for long-term adaptation in Spain are scarce. This study aims to explore temporal variations of the minimum mortality temperature and mortality burden from heat and cold between 1979 and 2018. Methods We collected individual all-cause mortality and climate reanalysis data for 4 decades at a daily time step. To estimate the temperature-mortality association for each decade, we fitted a quasi-Poisson time-series regression model using a distributed lag non-linear model with 21 days of lag, controlling for trends and day of the week. We also calculated attributable mortality fractions by age and sex for heat and cold, defined as temperatures above and below the optimum temperature, which corresponds to the minimum mortality in each period. Results We analysed over 14 million deaths registered in Spain between 1979 and 2018. The optimum temperature estimated at a nationwide scale declined from 21 °C in 1979–1988 to 16 °C in 1999–2008, and raised to 18 °C in 2009–2018. The mortality burden from moderate cold showed a 3-fold reduction down to 2.4% in 2009–2018. Since 1988–1999, the mortality risk attributable to moderate (extreme) heat reduced from 0.9% (0.8%) to 0.6% (0.5%). The mortality risk due to heat in women was almost 2 times larger than in men, and did not decrease over time. Conclusion Despite the progressively warmer temperatures in Spain, we observed a persistent flattening of the exposure-response curves, which marked an expansion of the uncertainty range of the optimal temperatures. Adaptation has been produced to some extent in a non-uniform manner with a substantial decrease in cold-related mortality, while for heat it became more apparent in the most recent decade only.