Although several new implants have been developed using animal studies for the treatment of osteochondral and cartilage defects, there is a lack of information on the possible metabolic and biochemical reactions of the body to the implantation of biomaterials and cartilage reconstruction. Therefore, this study was aimed at evaluating the serum protein pattern and the alterations in the concentrations of selected acute phase proteins in five clinically healthy female sheep before and after the reconstruction of experimentally induced articular cartilage defects using polyhydroxybutyrate/chitosan based biopolymer material. The concentrations of total serum proteins (TSP), protein fractions, and selected acute phase proteins—serum amyloid A (SAA), haptoglobin (Hp), and C-reactive protein (CRP)—were measured before and on days seven, 14, and 30 after the surgical intervention. The TSP concentrations showed no marked differences during the evaluated period. Albumin values decreased on day seven and day 14 after surgery. In the concentrations of α1-, α2-, β-, and γ2-globulins, a gradual significant increase was observed during the postoperative period (p < 0.05). The γ1-globulins decreased slightly seven days after surgery. The concentrations of SAA, Hp, and CRP increased significantly after the surgical intervention with a subsequent decrease on day 30. Presented results suggest marked alterations in the serum protein pattern after surgical intervention.