Magnesium sulfate (MgSO4) is a salt that has the potential to damage portland cement-based materials. This paper argues that the mechanism of damage is dependent on the concentration of MgSO4 and reports the results of the change in the micromechanical properties of calcium-silicate-hydrate (C-S-H) when exposed to different MgSO4 concentrations . Different concentrations were selected starting from the concentration found in seawater and increasing up to 20 g/l, which is the concentration considered for accelerated tests. The micromechanical properties of C-S-H were probed using nanoindentation; X-ray diffraction measurements were also performed on C-S-H specimens. A Mori-Tanaka homogenization scheme was employed to upscale these results, yielding two homogenization levels. At low MgSO4 concentrations (2.2 and 4 g/l) the formation of brucite and gypsum crystals in the pore solution contributes to the overall magnitude of the elastic modulus of the specimen, while at higher concentrations of MgSO4 (10 and 20 g/l), decalcification of C-S-H is observed, which results in the degradation of C-S-H micromechanical properties.