During the storage of spent polymer materials derived from municipal solid waste, which contain biodegradable impurities, an intense growth of microorganisms takes place. The aerobic metabolism of microorganisms may cause these materials to combust spontaneously and to become a real epidemiological risk for humans. The aim of the research is to determine the optimal addition of calcium oxide (CaO), which effectively reduces the number of selected microorganism groups populating the analyzed materials, in which spent polymers represent a significant fraction: refuse-derived fuel (RDF) and an undersize fraction of municipal solid waste (UFMSW). The main novelty of the experiments is to assess the benefits of using the commonly available and cheap filler (CaO), to hygienize the material and to reduce the fire hazard arising from its storage. During the mixing of spent polymer materials with pulverized CaO (mass shares: 1, 2, and 5% CaO), temperature changes were monitored using thermography. Moisture content (MC), pH, respiration activity (AT4) and bacterial count were determined before and after the experiment. During the addition of CaO (especially when the content was at 5%) to the UFMSW, higher maximum temperatures were obtained than in the case of RDF analyses, which may be the result of a high percentage of the biodegradable fraction and higher MC of the UFMSW. In all cases the waste temperature did not increase again after 3 min. CaO used in the experiment effectively limited the number of microorganisms. The addition of 5% of CaO has showed the strongest antimicrobial properties, and it can be recommended for hygienization of the analyzed materials and for the reduction of the risk of self-heating during their storage in windrows.