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Background: There is growing evidence that cancer patients may be more susceptible to contracting coronavirus disease 2019 (COVID-19) infection, show a more aggressive course and associate a poorer prognosis than the general population An unbalanced inflammatory response and systemic coagulopathy seem to define the pathological hallmark underlying severe presentations However, the complex immune cell interplay and the role of the tumor-associated pro-coagulative state in COVID-19 remain a challenge Methods: We prospectively evaluated cancer patients presenting to the emergency department of the Hospital Clinico San Carlos (Madrid, Spain) with severe pneumonia, and compared a comprehensive coagulation and immunological profile from blood samples on admission between those with SARS-CoV-2 positive and negative RT-PCR tests Results: 14 patients with suspected COVID-19 and receiving in-hospital care were prospectively followed SARS-CoV-2 RT-PCR was positive on admission in 6 patients, and negative on admission and on re-test in 8 patients Peripheral blood samples were drawn on admission In spite of the modest sample size, patients with SARS-CoV-2 positive showed higher levels of D-dimer (median 6,355 vs 1,964 ng/ml, p=0 025), a decreased CD4+/CD8+ ratio (1 2 vs 2 2, p=0 17) at the expense of CD4+ T lymphocytopenia (305 vs 467, p=0 18), and NK cell expansion (17 vs 9%, p=0 13) Several monocyte activation markers were found to be elevated in RT-PCR positive patients, including CD86 (2 8-fold increase in classic monocytes, p=0 06) and CCR2 (2 9-fold in intermediate monocytes, p=0 17;11-fold in non-classic monocytes, p=0 03) Conclusions: In cancer patients presenting with severe SARS-CoV-2 positive pneumonia, the infection may cause a hypercoagulable state, as suggested by higher levels of D-dimer, and unleash a pro-inflammatory response Marked CD4+ T lymphocytopenia and NK expansion may reflect lymphocyte exhaustion and dysregulated cytotoxicity Monocyte activation and recruitment also seem to be strongly upregulated Legal entity responsible for the study: Hospital Clinico San Carlos Funding: Cris Cancer Foundation Disclosure: All authors have declared no conflicts of interest