Background: Total knee arthroplasty is associated with an inflammatory response and high levels of pain in a subset of patients. Pain catastrophizing has been associated with acute postoperative pain. The association between these variables has not been investigated in an optimised fast-track setup including preoperative glucocorticoids. The aim of this study was, first, to investigate the correlation between the increase in postoperative c-reactive protein (CRP) and acute postoperative pain after total knee arthroplasty, and second, to investigate the correlation between the increase in CRP and preoperative pain catastrophizing. Methods: This study is a secondary analysis of data from 119 patients participating in two randomised controlled trials. Correlation analyses were performed for preoperative CRP and CRP increase at 24 and 48 h and pain during a well-defined mobilisation at 24 and 48 h after total knee arthroplasty. Additionally, correlation analyses were performed between CRP increase and pain catastrophizing using the pain catastrophizing scale. Results: There was no correlation between preoperative CRP or postoperative CRP increase and pain at both 24 and 48 h. Analyses were similar when separated into high and low pain catastrophizers. There was no correlation between preoperative CRP or postoperative CRP increase and pain catastrophizing. Conclusion: There was no association between the postoperative CRP response and postoperative acute pain or pain catastrophizing in patients undergoing total knee arthroplasty in a well-defined multimodal fast-track regime including preoperative glucocorticoids. These results suggest that acute pain after knee arthroplasty is not reflected by CRP when applying preoperative glucocorticoids.