The COVID-19 pandemic, caused by the infectious agent SARS-CoV-2, has claimed the life of thousands of people around the world following its rapid expansion from Wuhan, China, in early January 2020. Since then, multiple groups worldwide have attempted to describe predictive models for adverse clinical outcomes in patients affected by this disease. Within laboratory findings, the first Chinese cohorts described an inverse relationship between the absolute lymphocyte count and disease severity, and about 80% of severe patients exhibited lymphopenia. However, there are discrepancies regarding the predictive value of this clinical manifestation, as well as in the pathophysiological mechanisms involved. Here, we review current evidence regarding lymphopenia in patients with COVID-19, and the potential utility of this hematological finding as a disease biomarker.