Dexmedetomidine‐associated fever has been reported in the literature and can lead to lengthy workups and unnecessary antibiotic exposure. We conducted a systematic review to evaluate and describe the evidence of fever or hyperthermia caused by dexmedetomidine in adult patients. Data sources included PubMed/MEDLINE, EMBASE, CINAHL, and Web of Sciences. English‐language studies of any design published from inception through April 2020 including conference abstracts were included. The target population was hospitalized adult patients. Quality of evidence was determined based on GRADE recommendations and risk of bias assessed using the Evidence Project Risk of Bias tool. Naranjo scores were assessed to determine the likeliness of adverse event being caused by dexmedetomidine. All data were extracted independently and with the guidance of a medical librarian. Four hundred and eighty‐eight total citations were found on formal search, with 329 left after removal of duplicates. Independent record screening was performed, leaving 17 citations including 4 retrospective cohort studies, 1 case series, and 12 case reports. Quality of evidence ranged from very low to low for identified analyses. Evidence with patient‐level data (case reports and series) were combined to establish a cohort for descriptive results. The median Naranjo score was 4 (range, 3 to 8), and dexmedetomidine doses ranged from 0.1 to 2 μg·h/kg. Obesity and cardiac surgery appear to be significant risk factors. Dexmedetomidine‐associated fever appears uncommon, but the true incidence is unknown. Clinicians should keep dexmedetomidine‐associated fever in their differential, and stewardship programs should consider assessing for this adverse effect in their patient monitoring.