Abstract Hemostatic effects of oxidized cellulose are well known but the mechanism of its action is far from being well understood. Hemostatic (hemostyptic) biomaterials with their ability to initiate or accelerate thrombus formation belong to surgical sealants. Thrombus formation is a surface phenomenon. The exploitation of surface plasmon resonance sensing principle for the examination of interactions of oxidized cellulose with fibrinogen, fibrin and blood platelets is reported. Cellulose decreased and slowed down the interaction of immobilized fibrin monomer with fibrinogen as observed by surface plasmon resonance. Only weak interactions of cellulose with plasma proteins albumin and fibrinogen were observed. Delayed gelation and slower increase in turbidity occurred in fibrinogen–thrombin solutions in the presence of the cellulose. Platelets in plasma but not washed platelets in a buffer were activated in the presence of cellulose. We suppose that activation of the coagulation contact system of blood plasma initiated very likely by the negatively charged surface of the oxidized cellulose leads to the fibrin formation and activation and adhesion of blood platelets. The direct interactions of platelets and fibrinogen with the cellulose seem to play a secondary role.