BackgroundC‐reactive protein (CRP) is an acute‐phase protein produced by the liver during systemic inflammation. In humans, some epilepsies are associated with increased serum CRP (sCRP) concentrations, but this has yet to be proven in veterinary studies. Dogs with structural epilepsy (SE) and normal interictal neurological examination are hard to distinguish from dogs with idiopathic epilepsy (IE) without the use of advanced imaging.MethodsThe study included eight dogs with SE and 12 dogs with IE from a referral hospital population. This was a retrospective observational cohort study. The Mann–Whitney test was used to compare the sCRP concentrations within 24 hours of the last epileptic seizure between dogs with SE or IE.ResultsDogs with SE had higher sCRP concentrations than dogs with IE (8.9 [range <2.2–53.2] mg/L vs. <2.2 [range <2.2–6.9] mg/L; p = 0.043). Five of the eight (62%) dogs with SE had an sCRP concentration above the reference interval, compared with none of the 12 dogs with IE.LimitationsThe small sample size was the major limitation of this study. Other inflammatory causes were also not exclusively ruled out, although further clinical investigations were not indicated.ConclusionsThis study found that sCRP concentrations were higher in this cohort of dogs with SE than in those with IE. Further studies with larger cohorts of dogs are warranted to validate if sCRP can be used as an additional biomarker for SE.