Aim: Hypothermia is a rare but serious complication of antipsychotic drugs that can result in death. In this study, we aimed to investigate body temperature alterations in acute phase of chlorpromazine treatment, the relationship of inflammatory indicators and risk factors for hypothermic effect on intensive care unit (ICU) patients. Materials and methods: 63 intensive care patients who needed sedative treatment due to agitation were divided into two groups as Group 1 (n = 30) with temperatures ≤ 38°C, and Group 2 (n = 33) with temperatures > 38°C according to baseline body temperatures. Also, recurrent measurements for 12 hours were made at specific intervals following 25 mg intravenous chlorpromazine. Results: In Group 1, decrease in body temperatures was significant from 4th to 12th hours (p < 0.01), while in Group 2, significant decreases in body temperatures at all measurement hours were observed (p < 0.01). Temperature changes (delta temperature) observed at specific measurement intervals were significantly higher in Group 2 compared to Group 1. That difference was statistically significant at all intervals except for ΔTemperature B-6 (p < 0.05). The odds of hypothermic effects by chlorpromazine were 16%, 46%, 3%, and 18% for Acute Physiology and Chronic Health Evaluation II, procalcitonin, C-reactive protein, and white blood cells, respectively. Conclusion: Chlorpromazine treatment applied for agitation in ICU patients was associated with acute hypothermic effect. Severity of disease and comorbidities might increase risk of hypothermia, and inflammatory biomarkers might be predictors of adverse drug reaction.