We have examined the heat and cold-related mortality risk subject to cold and heat extremes by using a generalized additive model (GAM) regression technique to quantify the effect of the stimulus of mortality in the presence of covariate data for 2007–2014 in Nicosia, Cyprus. The use of the GAM technique with multiple linear regression allowed for the continuous covariates of temperature and diurnal temperature range (DTR) to be modeled as smooth functions and the lag period was considered to relate mortality to lagged values of temperature. Our findings indicate that the previous three days’ temperatures were strongly predictive of mortality. The mortality risk decreased as the minimum temperature (T_min) increased from the coldest days to a certain threshold temperature about 20–21°C (different for each age group and gender), above which the mortality risk increased as T_min increased. The investigated fixed factors analysis showed an insignificant association of gender-mortality, whereas the age-mortality association showed that the population over 80 was more vulnerable to temperature variations. It was recommended that the minimum mortality temperature is calculated using the minimum daily temperatures because it has a stronger correlation to the probability for risk of mortality. It is still undetermined as to what degree a change in existing climatic conditions will increase the environmental stress to humans as the population is acclimatized to different climates with different threshold temperatures and minimum mortality temperatures.