Patients with coronary artery disease (CAD) are at risk of life-threatening heart and lung injury, major complications of SARS-CoV-2 infection. Monocytes are critically involved in the immuno-response of inflammatory diseases. Intensified risk assessment might improve outcome during SARS-CoV-2 infection. We prospectively studied a cohort of 96 participants comprising 47 consecutive patients with CAD and acute SARS-CoV-2 infection (CAD+SARS-CoV-2), 19 CAD patients without infections, and 30 healthy controls. Clinical assessment included blood sampling, echocardiography, and electrocardiography within 12 hours of admission. Respiratory failure was stratified by the Horovitz Index (HI) as moderately/severely impaired when HI ≤ 200mmHg. The clinical endpoint (EP) was defined as HI ≤ 200mmHg with subsequent mechanical ventilation within a follow-up of 30 days. The numbers of CD14^dimCD16⁺ non-classical monocytes in peripheral blood were remarkably low in CAD+SARS-CoV-2 compared to CAD patients without infection and healthy controls (p<0.0001). These CD14^dimCD16 monocytes showed decreased expression of established markers of adhesion, migration, and T cell activation (CD54, CD62L, CX3CR1, CD80, HLA-DR) suggesting impaired function of the remaining CD14^dimCD16⁺ monocytes. Decreased numbers of CD14^dimCD16⁺ monocytes were associated with the occurrence of EP. Kaplan-Meier curves illustrate that CAD+SARS-CoV-2 patients with numbers below the median of CD14^dimCD16⁺ monocytes (median 1443 cells/mL) reached EP significantly more often compared to patients with numbers above the median (log-rank 5.03, p=0.025). Decreased numbers of CD14^dimCD16⁺ monocytes are associated with rapidly progressive respiratory failure in CAD+SARS-CoV-2 patients. Intensified risk assessments comprising monocyte sub- and phenotypes may help to identify patients at risk for respiratory failure.