A plastic optical fibre biosensor based on surface plasmon resonance for the detection of C-reactive protein (CRP) in serum is proposed. The biosensor was integrated into a home-made thermo-stabilized microfluidic system that allows avoiding any thermal and/or mechanical fluctuation and maintaining the best stable conditions during the measurements. A working range of 0.006-70 mg L and a limit of detection of 0.009 mg L were achieved. These results are among the best compared to other SPR-based biosensors for CRP detection, especially considering that they were achieved in a real and complex medium, i.e. serum. In addition, since the sensor performances satisfy those requested in physiologically-relevant clinical applications, the whole biosensing platform could well address high sensitive, easy to realize, real-time, label-free, portable and low cost diagnosis of CRP for future lab-on-a-chip applications. 3D sketch (left) of the thermo-stabilized home-made flow cell developed to house the SPR-based plastic optical fibre biosensor. Exemplary response curve (shift of the SPR wavelength versus time) of the proposed biosensor (right) for the detection of C-reactive protein in serum.