The pressure (100–200 MPa) and temperature (900–1100°C) effects on the equilibria of native point defects and background impurities in Zn-enriched ZnS are studied using cathodoluminescence and transmission spectra. The optimal conditions are found under which high pressures and temperatures accelerate migration of defects and impurities. The associated structural and compositional changes are studied by scanning electron microscopy. The increase in the concentration of dissolved oxygen at high pressures and temperatures is accompanied by a reduction in the band gap of ZnS, growth and blue shift (to 395–400 nm) of the shorter wavelength component of the SA blue emission in ZnS, and quenching of the longer wavelength component (445 nm). In addition, at 300 K a free-exciton bandI1 emerges at 342 nm. It is shown that the data available in the literature can be used to evaluate the concentration of dissolved oxygen in ZnS · O from its band gap. The effects of different oxygen species on the transmission of ZnS are studied in the range 3.5–15 μm.