AbstractPlasmonic biosensors have demonstrated versatility across diverse applications, including clinical diagnostics, environmental monitoring, and food analysis. Multiplexed plasmonic biosensors capable of detecting multiple analytes simultaneously have also been developed. However, existing designs face challenges for wide‐scale adoption due to bulky designs and expense. A compact multichannel plasmonic biosensor platform is presented for multiplexed detection of up to four biomarkers from one sample distributed via microfluidic channels. The device operates under the Kretschmann configuration for sequential quasi‐simultaneous multichannel sensing. Optical performance evaluation demonstrates high sensitivity and a limit of detection (LOD) of 10⁻⁶ RIU across four channels. The biosensing capabilities of the device have been assessed for detecting four inflammatory biomarkers. Customized biofunctionalization of sensor chips ensures inter‐channel reproducibility and direct binding detection assays for C‐reactive protein (CRP), interleukin‐6 (IL‐6), procalcitonin (PCT), and pancreatic stone protein (PSP), with sensitivities in the low ng/mL range and negligible cross‐reactivity. Recovery testing confirms its feasibility for detecting multiple biomarkers at low concentrations in human serum. The compact, user‐friendly design makes this biosensor an attractive tool for multiplexed detection, underscoring its applicability beyond inflammatory‐related processes, offering a versatile solution for biomarker analysis in human fluids, and contributing to the decentralization of diagnostics for complex diseases.