The enduring SARS-CoV-2 pandemic necessitates robust tools for severity assessment. This study, conducted at Islamabad Diagnostic Center across Pakistan from January 2021 to August 2022, aimed to investigate hematological abnormalities among suspected SARS-CoV-2 subjects. Initial enrollment included 130,347 cases, with 53,078 confirmed positive and 77,269 negative. An additional 11,786 samples expanded the dataset to 142,133. The Omicron and Centaurus variants, in confirmed positive patients, exhibited a slightly higher frequency of hematological abnormalities (30.42%) than negative participants (27.01%). Notably, lymphocyte count reduction (40.95%) suggested its potential as an alternative diagnostic parameter for clinical COVID-19. Decreased levels of NA (37.99%), HGB (26.17%), MCV (20.60%), PLT (6.15%), and ALB (2.28%) were observed. Abnormally elevated NEU, CR, MONO, RBCs, WBC, and EOS levels affected 26.00%, 24.28%, 30.79%, 22.02%, 6.28%, and 5.53% of subjects, respectively. Comparatively, positive patients exhibited higher abnormal blood parameters—LYMP count (57.40%), NEU count (46.08%), EOS count (62.48%), MONO count (31.61%), RBC count (30.32%), ALC count (43.60%), CR count (30.91%), NA count (40.53%), CRP count (68.46%), and DD (63.08%) than negative counterparts. The study underscores lymphocytopenia’s potential as a cost-effective, early diagnostic biomarker for clinical COVID-19, preceding real-time PCR diagnosis. This supports its consideration in resource-limited settings for strategic screening and policy-making in the ongoing SARS-CoV-2 battle.