This guidance document outlines an approach to leverage existing surveillance systems for Severe Acute Respiratory Infection (SARI) to estimate COVID-19 vaccine effectiveness (VE) in preventing SARI associated with laboratory-confirmed SARS-CoV-2 using existing SARI surveillance systems. The approach uses the test-negative design to evaluate VE; cases are SARI patients who tested positive for SARS-CoV-2, and controls are SARI patients who tested negative for SARS-CoV-2.This document is intended to be used as a guidance document to support countries and institutions that are interested in conducting research on COVID-19 vaccine effectiveness in SARI patients. It outlines an approach to post-introduction COVID-19 vaccine effectiveness evaluation in SARI patients that complements existing WHO Unity Studies, which focus on sero-epidemiological investigations. Research should be conducted only after site-specific protocols are developed and approved by the relevant local ethical review committee(s).