Introduction: A large proportion of patients with infectious mononucleosis (IM) have abnormal liver function tests (LFT) at presentation. There is no guideline regarding the management and follow-up of these patients. Some patients also have abdominal ultrasound due to deranged LFT, the need for this practice is unclear. The aim of this systematic review was to evaluate the evidence base on LFT assessment in IM, time to resolution of derangement, and the role of abdominal ultrasound. Methods: A systematic search of PubMed, EMBASE and the Cochrane library was done. Two authors independently screened records for eligibility using pre-defined criteria. We included both adult and paediatric populations. Quality assessment of included studies was done. Results: A total of 3924 patients were included from 32 studies. A combination of typical clinical features, heterophile antibodies and EBV-specific antibodies were used to ascertain diagnosis. The following proportion of patients had abnormal LFTs: AST (57%); ALT (62%); ALP (65%); Bilirubin (16%); GGT (41%). Reported median (i.q.r.) time to resolution of LFT was 8 (6–12) weeks. Maximum time to resolution was >6 months. Clinical hepatomegaly and splenomegaly were found in 35% and 44% of patients respectively. Enlarged liver and spleen on ultrasound were seen in 16/29 (55%) and 38/38 (100%) of patients respectively. There were no reports of decompensated liver disease. Conclusion: Derangement in LFTs can persist over six months from initial presentation in IM. However, this is self-limiting. The evidence suggests serial liver function assessments and ultrasound abdomen are not required in immunocompetent patients with subclinical derangement in LFTs.