Abstract <p>Low efficiency of metal mixing in the interstellar gas leads to the fact that their inhomogenous spatial distribution persist in the medium for a long time. In this paper, we study the effect of variations in the elemental composition on the chemical evolution of molecular gas cooling behind the fronts of shock waves from supernovae. Numerical modeling of nonequilibrium chemical kinetics for the Lagrangian element of gas behind shock waves with velocities of 5–15 km/s is performed. The abundance of carbon and oxygen varied within ±0.3 dex from the characteristic values for the interstellar medium of the Galaxy. Significant deviations in the fractions of some molecules are found that are not proportional to the change in the abundance of the corresponding chemical elements. Moreover, these deviations significantly exceed the initial variations in the abundances of elements. The dependence of the deviation in the molecular fractions on the gas properties and external effects, such as: gas density, ultraviolet radiation flux, ionization rate by cosmic rays, and extinction is studied. With a variation in the oxygen abundance of δ[O/H] ∼ ±0.3 dex, the fractions of water molecules deviate from the corresponding value during evolution for the interstellar adundance by a factor of ∼3−50. The deviations are most significant for extinction <i>A</i>_<i>V</i> ∼ 0.3 − 3. The importance of the variations for the chemical kinetics of molecules in star-forming regions is discussed.</p>