Background: Following tissue injury, the acute phase response (APR) functions to survive and then repair injured tissue. An exuberant APR, which can be evoked by total knee arthroplasty (TKA), results in a hyper-inflammatory state, leading to pain, nausea, venous thromboembolism, or potentially life-threatening complications. Here, we observed the effects of peri-operative dexamethasone on the APR following TKA by trending C-reactive protein (CRP, mg/L) and fibrinogen (mg/dL). We hypothesize that the anti-inflammatory effects of dexamethasone can attenuate the APR after TKA and will be associated with decreased post-operative pain and nausea., Methods: A retrospective case-control study was performed on 188 unilateral TKA procedures. The patients were divided into a group receiving dexamethasone (10 mg intra-operatively and on post-operative day [POD] 1) and a group receiving no corticosteroids. Post-operative CRP, fibrinogen, morphine equivalents, and anti-emetic doses were recorded., Results: Compared to the non-steroid group, patients receiving dexamethasone yielded a significantly decreased CRP on POD0 (5.5 vs 8.3), POD1 (11.8 vs 22.0), and POD2 (85.5 vs 148.9). A significant decrease in fibrinogen in patients receiving dexamethasone was seen on POD2 (460.0 vs 530.2). There was an increase in fibrinogen within the dexamethasone cohort at the 2-week visit (535.4 vs 488.9). Post-operative morphine equivalents administered were significantly decreased in patients receiving dexamethasone, but no difference in anti-emetic use was appreciated., Conclusion: These data support the hypothesis that the APR following TKA can be attenuated pharmacologically by corticosteroids. Further studies are needed to determine whether the attenuation of the APR with the use of corticosteroids prevents complications following TKA., (Copyright © 2018 Elsevier Inc. All rights reserved.)