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<h4>Objectives</h4> To evaluate the prognostic value of the coefficient of variance of axial light loss of monocytes (cv-ALL of monocytes) for adverse clinical outcomes in patients suspected of infection in the emergency department (ED). <h4>Methods</h4> We performed an observational, retrospective monocenter study including all medical patients ≥18 years admitted to the ED between September 2016 and June 2019 with suspected infection. Adverse clinical outcomes included 30-day mortality and ICU/MCU admission <3 days after presentation. We determined the additional value of monocyte cv-ALL and compared to frequently used clinical prediction scores (SIRS, qSOFA, MEWS). Next, we developed a clinical model with routinely available parameters at the ED, including cv-ALL of monocytes. <h4>Results</h4> A total of 3526 of patients were included. The OR for cv-ALL of monocytes alone was 2.21 (1.98–2.47) for 30-day mortality and 2.07 (1.86–2.29) for ICU/MCU admission <3 days after ED presentation. When cv-ALL of monocytes was combined with a clinical score, the prognostic accuracy increased significantly for all tested scores (SIRS, qSOFA, MEWS). The maximum AUC for a model with routinely available parameters at the ED was 0.81 to predict 30-day mortality and 0.81 for ICU/MCU admission. <h4>Conclusions</h4> Cv-ALL of monocytes is a readily available biomarker that is useful as prognostic marker to predict 30-day mortality. Furthermore, it can be used to improve routine prediction of adverse clinical outcomes at the ED. <h4>Clinical trial registration</h4> Registered in the Dutch Trial Register (NTR) und number 6916.