Cardiogenic shock (CS) following an out-of-hospital cardiac arrest (OHCA) poses significant management challenges, exacerbated by inflammatory responses and infectious complications. This study investigates the microbiological profiles and impacts of mechanical circulatory support (MCS) on inflammation and infection in OHCA patients. We retrospectively analyzed microbiological data from various specimens of 372 OHCA patients, who were treated at the Cardiac Arrest Center of the University Hospital of Marburg from January 2018 to December 2022. Clinical outcomes were evaluated to investigate the potential impact of MCS on infection and inflammation. Of the study cohort, 115 patients received MCS. The microbiological analysis revealed a higher incidence of positive blood cultures in the MCS group vs. the non-MCS group (39% vs. 27.7%, = 0.037), with predominantly Gram-positive bacteria. Patients with positive microbiological findings had longer in-hospital stays and prolonged periods of mechanical ventilation. The levels of inflammatory markers such as C-reactive protein (CRP) and procalcitonin (PCT) differed, suggesting a more pronounced inflammatory response in MCS patients, especially in the later ICU stages. Notably, despite the higher infection rate in the MCS group, the survival rates did not significantly differ in the two groups. MCS appears to influence the microbiological and inflammatory landscape in OHCA patients, increasing the susceptibility to certain infections but not affecting the overall mortality. This study underscores the complexity of managing post-resuscitation care and highlights the need for tailored therapeutic strategies to effectively mitigate infectious and inflammatory complications.