Background: It is unclear whether fever suppression is beneficial or harmful in the long term in the elderly, due to different immune profile and body temperature compared to the young. Our objective was to determine the long-term health effects of antipyretic treatment in the elderly during infections.Methods: a systematic review was carried out including studies investigating antipyretic treatment during infections, comparing with any other drug/therapy/placebo/none. PubMed, Embase and Cochrane CENTRAL databases were searched. Primary and secondary outcomes were onset or worsening of chronic inflammatory diseases, and fever reduction, length of hospital stay, patient satisfaction, mortality, laboratory parameters indicative of morbidity and progress to complications respectively.Results: Of 11481, studies,17 (2 RCTs, 7 observational, 1 case series and 7 case reports) were included for the review. None investigated the primary outcome and patient-reported outcomes.Risk-of-bias of studies was unclear to high in the included studies. Narrative synthesis was performed as meta-analysis was impossible owing to heterogeneity of the included studies.Antipyretics showed significant reduction of fever in the RCTs. Five studies reported significant drop in BP and one study showed significant mortality from the antipyretics. Morbidity indicators and length of stay were available only in the studies that reported adverse events. Certainty of evidence (GRADE) was low to very low for all outcomes.Conclusions: Evidence regarding long term benefit or harm from fever suppression with antipyretics during infections in the elderly is insufficient.