This chapter discusses two microfluidic-based approaches for early sepsis detection that achieve a higher accuracy than traditional blood culture analysis. Patient blood samples were included in this work to validate the performance of our chips in diagnosing sepsis. The single-parameter chip demonstrated the increased accuracy if using CD64 as a biomarker for sepsis detection compared with C-reactive protein (CRP) and procalcitonin (PCT) when applied alone. In addition, a multiparameter chip measuring a combined panel of CD25, CD64, and CD69, and achieved a high accuracy with an Area Under the Receiver Operating Characteristic Curve (AUROC) of 0.978. The combined panel was also able to detect culture-negative patients and provided a faster diagnosis. Besides, microfluidics has advantages of less time consuming, easier to manufacture, less sample loading, less complex, and portable. Therefore, our approach is of great potential to become a bedside sepsis detection method.