BackgroundTemperature, precipitation, relative humidity (RH), and Normalized Different Vegetation Index (NDVI), influence malaria transmission dynamics. However, an understanding of interactions between socioeconomic indicators, environmental factors and malaria incidence can help design interventions to alleviate the high burden of malaria infections on vulnerable populations. Our study thus aimed to investigate the socioeconomic and climatological factors influencing spatial and temporal variability of malaria infections in Mozambique.MethodsWe used monthly malaria cases from 2016 to 2018 at the district level. We developed an hierarchical spatial–temporal model in a Bayesian framework. Monthly malaria cases were assumed to follow a negative binomial distribution. We used integrated nested Laplace approximation (INLA) in R for Bayesian inference and distributed lag nonlinear modeling (DLNM) framework to explore exposure-response relationships between climate variables and risk of malaria infection in Mozambique, while adjusting for socioeconomic factors.ResultsA total of 19,948,295 malaria cases were reported between 2016 and 2018 in Mozambique. Malaria risk increased with higher monthly mean temperatures between 20 and 29°C, at mean temperature of 25°C, the risk of malaria was 3.45 times higher (RR 3.45 [95%CI: 2.37–5.03]). Malaria risk was greatest for NDVI above 0.22. The risk of malaria was 1.34 times higher (1.34 [1.01–1.79]) at monthly RH of 55%. Malaria risk reduced by 26.1%, for total monthly precipitation of 480 mm (0.739 [95%CI: 0.61–0.90]) at lag 2 months, while for lower total monthly precipitation of 10 mm, the risk of malaria was 1.87 times higher (1.87 [1.30–2.69]). After adjusting for climate variables, having lower level of education significantly increased malaria risk (1.034 [1.014–1.054]) and having electricity (0.979 [0.967–0.992]) and sharing toilet facilities (0.957 [0.924–0.991]) significantly reduced malaria risk.ConclusionOur current study identified lag patterns and association between climate variables and malaria incidence in Mozambique. Extremes in climate variables were associated with an increased risk of malaria transmission, peaks in transmission were varied. Our findings provide insights for designing early warning, prevention, and control strategies to minimize seasonal malaria surges and associated infections in Mozambique a region where Malaria causes substantial burden from illness and deaths.