Malaria is a major health problem in many tropical and subtropical countries and in the south of Iran. In this study, due to the importance of the disease in Sistan and Baluchestan province, the influence of temperature, humidity, and rainfall on malaria has been evaluated in areas with a high incidence of malaria. Malaria incidence data were inquired from the Province Health Authority, and climatic variables were inquired from the Bureau of Meteorology from 2000 to 2012 and were analyzed on a monthly basis. Changes in incidence of malaria with climatic factors were analyzed by negative binomial regression by Stata 11, and the correlations were calculated with Minitab15 for determining the potential impact of meteorological variables with and without lags on malaria transmission. The incidence of malaria had a significant positive correlation with the average, minimum, and maximum monthly temperatures and a negative correlation with rainfall and low humidity (<60%). However, humidity >60% had a positive impact on incidence; as in the town of Chabahar after adjusting variables such as rainfall and temperature; every one percent increase in humidity caused a 4% increase in malaria incidence in the same month and a significant 6% increase in the next month. Temperature and humidity over 60% are effective climate parameters in the incidence of malaria. These factors should be considered in planning for controlling and preventing malaria.