Introduction: Despite the large number of analgesic drugs available currently, pain therapy is still a challenging issue for researchers and clinicians. The search for new drugs that could relieve patients from pain is not only justified, but also highly recommended. Objective: This study aimed to perform antinociceptive screening of 4 various 1,2,4-triazole-3-thione derivatives (TPB-2, TPB-4, TPF-32 and TPF-38) in the hot-plate test in mice, which is an experimental model allowing the testing of compounds alleviating acute thermal pain. Material and methods: Experimental verification of the antinociceptive effects of the tested compounds (administered intraperitoneally in a constant dose of 300 mg/kg) was performed in the hot-plate test in mice, by calculating maximum possible antinociceptive effects (MPAE in %) at 4 various pretreatment times (15, 30, 60 and 120 min.). Results: TPB-2 exerted strong antinociceptive effects with MPAE ranging between 18.54 – 35.43% in the hot-plate test. Similarly, TPF-32 exerted firmly established antinociceptive effects with MPAE ranging from 13.50 – 37.05%. In the case of TPB-4 and TPF-38, both compounds produced slight changes in MPAE in the hot-plate test in mice. These agents can be classified as virtually ineffective in the hot-plate test. Conclusions: The screening test revealed that TPB-2 and TPF-32 exerted a clear-cut antinociceptive effect in the hot-plate test in mice. If the results from this study were to be translated to clinical settings, both TPB-2 and TPF-32 might be beneficial drugs for pain relief in humans.