The performance of E-SMS (Etched Singlemode-Multimode-Singlemode) optical fiber structures as immunosensors has been assessed by the implementation of antibody/antigen immunoassays. Through this procedure it has been proven that E-SMS structures are effective and suitable optical platforms for label-free biosensing. Using the phase shift and tracking the wavelength response it was found that the fabricated E-SMS devices exhibited limits of detection (LOD) down up to concentrations of 0.2 mg/L of antigens in solution. This was achieved by coating the E-SMS with an antibody-based biolayer (goat IgG) that is able to determine the presence of anti-goat IgG antigen. Both a wavelength detection and a fast Fourier transform (FFT) analysis technique were used to perform this analysis. The FFT method showed similar results to those observed with the most traditional wavelength analysis, but with the advantage of a simpler detection system that makes unnecessary the use of sophisticated optical interrogators.