To determine whether serum C-reactive protein (CRP) concentration could be used to detect gallbladder rupture (GBR) prior to surgery in dogs undergoing cholecystectomy for treatment of gallbladder mucocele (GBM). 45 dogs that underwent cholecystectomy because of GBM at a companion animal referral hospital from 2017 to 2020. Electronic medical records were reviewed, and dogs were included if serum CRP concentration had been measured within 24 hours prior to cholecystectomy. Dogs were grouped as to whether the gallbladder was found to be ruptured or intact during surgery. Accuracy of using preoperative CRP concentration to predict GBR was compared with accuracy of abdominal ultrasonography and other preoperative blood tests. GBR was present in 15 dogs at the time of surgery. Median preoperative CRP concentration was significantly higher in dogs with GBR (15.1 mg/dL; interquartile range, 7.4 to 16.8 mg/dL) than in dogs with an intact gallbladder (2.65 mg/dL; interquartile range, 0.97 to 13.4 mg/dL). Sensitivity, specificity, and accuracy of using preoperative CRP concentration to predict GBR were 100%, 67%, and 78%, respectively. Measurement of preoperative CRP concentration provided excellent sensitivity and moderate specificity for detection of GBR in dogs undergoing cholecystectomy because of GBM. Accuracy of using preoperative CRP concentration for detection of GBR was not superior to the accuracy of preoperative abdominal ultrasonography. However, when CRP concentration was combined with results of ultrasonography, the sensitivity, specificity, and accuracy for detection of GBR were 100%, 93%, and 96%, respectively.