The compressive deformation characteristics of a commercially pure magnesium-based syntactic foam, manufactured by infiltration technique, were investigated. The influence of the interface between the hollow spheres and the matrix on the deformation behavior was analyzed. The interface was modified by using two different cooling conditions with (a) quenching after the complete infiltration and (b) cooling down in the casting machine, and by (c) an additional heat treatment after (a): normalizing at 500 °C for 120 min. It has been found that in each condition a reaction zone formed, which consisted of a depleted layer in the hollow sphere and an interface layer in the Mg matrix with gradually changing composition. Condition (a) resulted in the highest peak strength, while condition (c) leads to the formation of micropores, causing the decrease of the stiffness and peak strength.