BackgroundIn recent years, the shift from traditional face-to-face teaching methods to eLearning methods has shown to improve professional training, particularly for the health workers in achieving necessary specialised worker training. However, there is a insufficient evidence on the costs and cost-effectiveness of designing and deploying eLearning interventions for healthcare workers in low- and middle-income countries.MethodsThe study protocol was developed and reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The Cochrane Handbook for Systematic Reviews of Interventions will be used to guide the conduct of the proposed systematic review and meta-analysis. Systematic literature searches will be conducted using the EBSCOhost platform ( Academic Search Complete, ERIC, health source: nursing/academic edition, MEDLINE with Full Text, OpenDissertations), Google Scholar, and the following databases: Web of Science, PubMed and ProQuest databases, evaluating the cost and cost-effectiveness of e-learning interventions for healthcare workers in low- and middle-income countries. The searches will be open to peer-reviewed articles published in all languages and no restriction in publication year. We will further evaluate the cost-effectiveness by determining heterogeneity in the content, if feasible we will do a meta-analysis using Meta- Easy Excel software tools. We will use OR and 95% CIs as measures of effect for dichotomous outcomes. As for continuous outcomes, we will use standardised mean differences and 95% CIs. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach will be used to assess the certainty of the evidence across outcomes. PRISMA-P will be used to report the findings of this systematic review and meta-analysis.DiscussionThis systematic review target to deliver complete evidence of cost and the cost-effectiveness of eLearning interventions for healthcare worker training. The study will be disseminated through the publication of the manuscript and policy brief in an appropriate journal and shared with the relevant stakeholders through conference presentations, discussions and seminars.Protocol registrationPROSPERO ID: 271180