Background: Fever is extremely common in neurocritical care patients and is independently associated with a worse outcome. Non-steroidal anti-inflammatory drugs (NSAIDs) lower the hypothalamic set point temperature through the inhibition of prostaglandin E2 synthesis, and they constitute a second line of pharmacological treatment for temperature control. This systematic review aims to evaluate the effectiveness of DCF in reducing body temperature and its effects on brain parameters. Methods: A comprehensive search of several databases was run in November 2022 in Ovid EBM (Evidence Based Medicine) Reviews, Cochrane library, Ovid Medline and Scopus (1980 onward). The outcome of interest included DCF control of body temperature and its impact on cerebral parameters. Results: A total of 113 titles were identified as potentially relevant. Six articles met eligible criteria and were reviewed. DCF induce a reduction in body temperature (MD, 1.10 [0.72, 1.49],p< 0.00001), a slight decrease in ICP (MD, 2.22 [−0.25, 4.68] IC 95%;p< 0.08) as well as in CPP and MAP (MD, 5.58 [0.43, 10.74] IC 95%;p< 0.03). The significant heterogeneity and possibility of publication bias reduces the strength of the available evidence. Conclusions: Diclofenac sodium is effective in reducing body temperature in patients with brain injury, but data in the literature are scarce and further studies are needed to evaluate the benefits of DCF.