Bio-polymer networks have mechanical properties that can be remarkably different from those of most synthetic materials. One such property is the strain-hardening response that is exhibited by most biological tissues. Strain-hardening allows tissues to be soft and malleable during small perturbations while being hard and stiff when they are deformed beyond a certain limit, thus allowing them to maintain their structural integrity under large loads. Despite their manifest importance, basic questions related to the structure of these biopolymer networks, such as how they deform under stress, still remain unanswered. We have used “artificial” blood clots (fibrin networks) as a model system to investigate the structure of these bio-networks under stress deformation throughout the strain-hardening regime. By combining simultaneously rheology and Small Angle Neutron Scattering measurements (Rheo-SANS) we were able to correlate the internal structural changes occurring in the material to the macroscopic mechanical response. Our results will be discussed with respect to two recent theoretical models that have been proposed to explain strain-hardening.