Sepsis, an infectious disease affecting millions of people’s health worldwide each year, calls for urgent attention to an improvement of analytical devices. Chemiluminescence immunoassay is a typical diagnostic method utilized to assess the risk development of sepsis. However, due to its high-cost, delayed, and complicated procedure, the practical utilization is therefore undoubtedly limited, especially for point-of-care test. Herein, we fabricated for the first time an immunosensor based on dendritic copper nanostructures (CuNSs) combined with 4-aminobenzoic acid (4-AB, the diazonium salt) as antibody linker modified on a screen-printed graphene electrode for the early detection of the sepsis biomarker interleukin-6 (IL-6). The electrode fabrication is made by electrodeposition, thus eliminating the multistep of nanomaterial synthesis and time wasting. The resulting dendritic CuNSs significantly increase the effective surface area (1.2 times) and the sensor’s performance. The morphology of this combination was characterized using CV, EIS, SEM, EDX, and FTIR techniques. In the detection process, the appearance of IL-6 suppresses the current response of the redox probe indicator measured by differential pulse voltammetry due to the antibody-antigen complex. The subtraction of signal (Δ I ) was interpreted as IL-6 concentration. This sensor exhibited a linear range from 0.05 to 500 pg mL −1 with low detection limit of 0.02 pg mL −1 , proving a possibility for early sepsis screening. In addition, the established immunosensor can successfully quantify IL-6 in human serum sample, in which the results agreed well with those achieved using the standard approach, further showing high practical applicability of this developed immunosensor. Graphical abstract Highlights Immunosensor based on CuNSs combined with 4-AB for IL-6 was first demonstrated. Composite of CuNSs and 4-AB significantly enhanced the sensor’s performance. Extremely high sensitivity with excellent selectivity was achieved. The sensor fabricated by electrodeposition can eliminate the multistep of preparation. This sensor was reliable and triumphantly applied to quantify IL-6 in human serum.