Background: Association between weather and daily mortality has been well established in developed countries. However, little is known about this relationship in urban populations in sub-Saharan Africa. The climate in sub-Saharan Africa vary largely with the location, in the case of Nairobi, Kenya, it is characterized by a relatively large daily temperature ranges. Also, the weather variation in urban areas is related to the urban heat islands. Aims: The study aim was to describe the relationship between weather and daily mortality in Nairobi, Kenya, and assess the relationship by cause of death, age, and sex. Methods: The study used mortality data from the Nairobi Urban Health and Demographic Surveillance System and weather data was obtained from Kenya Meteorological Department. The study covered a population of about 60,000 during the period 2003-2008. The daily weather effect on mortality was assessed using time series Poisson regression models with distributed lag to model the delayed effect. Results: High temperatures were significantly associated with mortality in children and non-communicable disease deaths. All-cause mortality increase by 3.0% for shorter lags of same day and previous day for one degree decrease from 18oC. Mortality among older people and children under 5 years appeared most susceptible to cold compared to other age groups. Rainfall, in the lag period of one month, increased all-cause mortality in general, but was found strongly related to mortality among females. Low temperatures were associated with deaths due to acute infections, whereas rainfall was associated with all-cause, pneumonia and NCD deaths. Conclusions: The results support significant temperature-related mortality in Nairobi with differences by age, sex, and cause of death. The study finding points to the need for further research to establish a better understanding of the processes and mechanisms involved in order to develop preventive strategies.