Background Patients with hematological malignancies (HM) have a high risk of severe coronavirus disease 2019 (COVID‐19), also in the Omicron period. Material and methods Retrospective single‐center study including HM patients with severe acute respiratory syndrome Coronavirus 2 (SARS‐CoV2) infection from January 2022 to March 2023. Study outcomes were respiratory failure (RF), mechanical ventilation (MV), and COVID‐related mortality, comparing patients according to SARS‐CoV2 serology. Results Note that, 112 patients were included: 39% had negative SARS‐CoV2 serology. Seronegative were older (71.5 vs. 65.0 years, p = 0.04), had more often a lymphoid neoplasm (88.6% vs. 69.1%, p = 0.02), underwent anti‐CD20 therapy (50.0% vs. 30.9% p = 0.04) and had more frequently a severe disease (23.0% vs. 3.0%, p = 0.02) than seropositive. Kaplan‐Meier showed a higher risk for seronegative patients for RF (p = 0.014), MV (p = 0.044), and COVID‐related mortality (p = 0.021). Negative SARS‐CoV2 serostatus resulted in a risk factor for RF (hazards ratio HR 2.19, 95% confidence interval CI 1.03–4.67, p = 0.04), MV (HR 3.37, 95% CI 1.06–10.68, p = 0.04), and COVID‐related mortality (HR 4.26, 95% CI 1.09–16.71, p = 0.04). Conclusions : HM patients with negative SARS‐CoV2 serology, despite vaccinations and previous infections, have worse clinical outcomes compared to seropositive patients in the Omicron era. The use of serology for SARS‐CoV2 diagnosis could be an easy tool to identify patients prone to developing complications.