Varicella is a highly contagious disease caused by the varicella zoster virus (VZV). While the disease is usually mild, severe complications can occur requiring costly hospitalization. A thorough understanding of the healthcare resource use (HCRU) and costs of varicella is needed to inform health-economic models of preventive strategies. A systematic literature review was carried out to retrieve relevant publications between 1999 and 2021, reporting HCRU and cost outcomes for varicella and its complications. Data were extracted and stratified according to pre-specified age groups and complication categories. Costs were re-based to a $US2020 footing using both purchasing power parity and the medical component of consumer price indexes. Data were summarized descriptively due to high heterogeneity in study design and outcome reporting. Forty-four publications fulfilled the inclusion and exclusion criteria of which 28 were conducted in Europe, 6 in Middle East and Asia, 5 in South America, 3 in North America, and 2 in multiple regions. Primary healthcare visits accounted for 30% to 85% of total direct costs. Hospitalization costs varied between $1,308 and $38,268 per episode depending on country, complication type, and length of stay, contributing between 2% and 60% to total direct costs. Indirect costs, mostly driven by workdays lost, accounted for approximately two-thirds of total costs due to varicella. The management of varicella and related complications can lead to substantial HCRU and costs for patients and the healthcare system. Additional research is needed to further characterize the varicella-associated economic burden and its broader impact from a societal standpoint.