Background: Considering the lack of research over this region the Statistical Downscaling Model (SDSM) was used as a tool for downscaling meteorological data statistically over four representative regions in the eastern side of Colombia. Data from the two Global Climate Models CanESM2 and IPSL-CM5A-MR, which are part of the CMIP5-project have been used to project future maximum and minimum temperature, precipitation and relative humidity for the periods 2021–2050 and 2071–2100. For both models, the Representative Concentration Pathways RCP2.6 and RCP8.5 were considered, representing two different possible future emission trajectories and radiative forcings. Predictor variables from the National Centre for Environmental Prediction (NCEP-DOE 2) reanalysis dataset, together with analyzed correlation coefficient (R) and root mean square error (RMSE) were used as performance indicators during the calibration and validation process. Results: Results indicate that Maximum and minimum temperature is projected to increase for both Global Climate Models and both Representative Concentration Pathways; relative humidity shows a decreasing trend for all scenarios and all regions; and precipitation shows a slight decrease over three regions and an increase over the warmest region. As expected, the results of the simulation for the period 2071–2100 show a more drastic change when compared to the baseline period of observations. Conclusions: The SDSM model proves to be efficient in the downscaling of maximum/minimum temperature as well as relative humidity over the studied regions; while showing a lower performance for precipitation, agreeing with the results for other statistical downscaling studies. The results of the projections offer good information for the evaluation of possible future-case scenarios and decision-making management.