This study focuses on CO2 diffusivity, which is one of the most important factors impacting eye growth in semi-hard cheese, but yet has scarcely been investigated in literature. The effect of compositional and ripening parameters on experimental CO2 diffusivity in semi-hard cheese was studied. CO2 diffusivity in semi-hard cheese showed a complex relationship with temperature in the range 4–25°C, represented by a quadratic curve with the highest diffusivity at 13°C. Salt was found to impact CO2 diffusivity, with a decrease of about 60% for 0–2.7% w/w salt addition, which may be ascribed to viscosity increase of the cheese matrix and “salting in” effect of protein. CO2 diffusivity was found to increase with moisture content from 39% to 42% w/w, then it decreased from 42% to 48% w/w. Inevitable changes in protein content of the three cheese variants may be responsible for the complex behaviour observed.