Introduction: Coronavirus disease 2019 (COVID-19) is characterized by a high contagiousness requiring isolation measures. At this time, diagnosis is based on the positivity of specific RT-PCR and/or chest computed tomography scan, which are time-consuming and may delay diagnosis. Complete blood count (CBC) can potentially contribute to the diagnosis of COVID-19. We studied whether the analysis of cellular population data (CPD), provided as part of CBC-Diff analysis by the DxH 800 analyzers (Beckman Coulter), can help to identify SARS-CoV-2 infection. Methods: Cellular population data of the different leukocyte subpopulations were analyzed in 137 controls, 322 patients with proven COVID-19 (COVID+), and 285 patients for whom investigations were negative for SARS-CoV-2 infection (COVID−). When CPD of COVID+ were different from controls and COVID− patients, we used receiver operating characteristic analysis to test the discriminating capacity of the individual parameters. Using a random forest classifier, we developed the algorithm based on the combination of 4 monocyte CPD to discriminate COVID+ from COVID− patients. This algorithm was tested prospectively in a series of 222 patients referred to the emergency unit. Results: Among the 222 patients, 86 were diagnosed as COVID-19 and 60.5% were correctly identified using the discriminating protocol. Among the 136 COVID− patients, 10.3% were misclassified (specificity 89.7%, sensitivity 60.5%). False negatives were observed mainly in patients with a low inflammatory state whereas false positives were mainly seen in patients with sepsis. Conclusion: Consideration of CPD could constitute a first step and potentially aid in the early diagnosis of COVID-19. © 2020 John Wiley & Sons Ltd