Sepsis is a major cause of mortality among hospitalized patients worldwide. Rapid diagnosis is critical as early treatments have been demonstrated to improve survival. Despite the importance of early detection, current technologies and clinical methods are often insufficient due to their lack of the necessary speed, selectivity, or sensitivity. The development of rapid sensing platforms that target sepsis-related biomarkers could significantly improve the outcomes of patients. This Mini-Review focuses on the recent advances in rapid diagnosis of soluble biomarkers in blood with the emphasis on different configurations of point-of-care (POC) instruments. Specifically, it first describes the commonly targeted biomarkers and the mechanisms by which they are detected. Then, it highlights the recently developed sensors that aim to reduce the total time of diagnosis without sacrificing selectivity and limit of detection. These sensors are categorized based on their distinct sensing and transduction mechanisms. Finally, it concludes with a brief outlook over future developments of multiplexed sensors.