Seasonal influenza affects a considerable proportion of the global population each year. We assessed the association between subnational influenza activity and temperature, specific humidity and rainfall in three Central America countries, i.e. Costa Rica, Honduras and Nicaragua. Using virologic data from each country's national influenza centre, rainfall from the Tropical Rainfall Measuring Mission and air temperature and specific humidity data from the Global Land Data Assimilation System, we applied logistic regression methods for each of the five sub-national locations studied. Influenza activity was represented by the weekly proportion of respiratory specimens that tested positive for influenza. The models were adjusted for the potentially confounding co-circulating respiratory viruses, seasonality and previous weeks' influenza activity. We found that influenza activity was proportionally associated (P<0.05) with specific humidity in all locations [odds ratio (OR) 1.21-1.56 per g/kg], while associations with temperature (OR 0.69-0.81 per °C) and rainfall (OR 1.01-1.06 per mm/day) were location-dependent. Among the meteorological parameters, specific humidity had the highest contribution (~3-15%) to the model in all but one location. As model validation, we estimated influenza activity for periods, in which the data was not used in training the models. The correlation coefficients between the estimates and the observed were ≤0.1 in 2 locations and between 0.6-0.86 in three others. In conclusion, our study revealed a proportional association between influenza activity and specific humidity in selected areas from the three Central America countries.