Objective To evaluate C‐reactive protein at presentation and during hospitalisation in dogs with acute kidney injury resulting from leptospirosis to compare C‐reactive protein at presentation in dogs with acute kidney injury of different aetiology and to study its correlation with markers of inflammation, azotaemia and survival. Materials and Methods Prospective observational study of 41 dogs with acute kidney injury secondary to leptospirosis and 15 control dogs with acute kidney injury of different aetiology. C‐reactive protein was measured at presentation in both groups and daily for 7 days in a subgroup of 28 dogs with leptospirosis. The associations of C‐reactive protein with neutrophil count, albumin, urea, creatinine and survival were analysed. Results C‐reactive protein was increased at presentation in all dogs with leptospirosis but was not significantly different from dogs with acute kidney injury of different cause. It was associated with markers of inflammation (neutrophil count, albumin) but not with azotaemia (creatinine, urea). It decreased gradually from presentation to day 4, with significantly lower concentrations in survivors than non‐survivors. Initial C‐reactive protein was only weakly associated with outcome, but its average concentration from presentation to day 2 was more strongly associated. Absolute and relative changes in C‐reactive protein during hospitalisation and creatinine at presentation were not associated with survival. Clinical Significance Serial assessment of C‐reactive protein may improve outcome prediction in dogs with leptospirosis compared with a single measurement at presentation or with markers of renal function.