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In today’s medicine, the celerity of the bio-assays analysis is crucial for the timely selection of the appropriate therapy and hence its effectiveness, especially in case of diseases characterized by the late onset of symptoms. In this paper, a lens-less fiber optics-based fluorescence sensor designed for the measurement of labeled bio-assays is presented and its potential for the early diagnosis of sepsis via C-reactive protein (CRP) detection is demonstrated. The sensor performance results from the combination of two key elements: a planar antenna that redirects fluorescence the marker emission and an automated fiber-based optical system for multi-spot analysis. First, the working principle of the device is demonstrated with a well-established antibody–antigen format (immunoglobulin IgG/anti-IgG assay), reporting more than one order of magnitude enhanced limit of detection (LOD) and limit of quantification (LOQ) for the planar antenna with respect to a standard glass substrate. The prototype is then tested against a sample mimicking a realistic case, prepared with commercially available human serum, showing a LOD and LOQ in the clinical range of interest (0.0015 μg/mL and 0.005 μg/mL, respectively) for the investigation of the sepsis biomarker CRP. These results validate the developed prototype as a simple and easy-to-operate device, compatible with standardized micro-well arrays, and potentially suitable for POC applications.