Objective -To evaluate C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-␣) kinetics in dogs with a systemic inflammatory response syndrome (SIRS) presented to an emergency service. We hypothesized serum CRP concentrations would increase and vary during hospitalization, and would correlate with plasma IL-6 and TNF-␣ concentrations, vary in magnitude according to the underlying disease, and predict survival. Design -Prospective, observational, clinical study. Setting -University emergency department. Animals -Sixty-nine dogs with SIRS weighing over 5 kg who could tolerate the blood sampling. Interventions -Serum and plasma were collected (and stored at -80°C) at presentation (T0), after 6 (T6), 12 (T12), 24 (T24), and 72 (T72) hours, and at a follow-up visit at least 1 month after discharge (T1m). Underlying diseases were categorized as infection (I), neoplasia (N), trauma (T), gastric-dilation and volvulus (GDV), other gastrointestinal (GI), renal (R), and miscellaneous (M) disease. Measurements and Main Results -Serum CRP concentration was measured using a canine-specific immunoturbidimetric assay. Biologically active plasma IL-6 and TNF-␣ concentrations were assessed using bioassays. Forty-four dogs survived, 8 died, and 17 were euthanized. Nineteen dogs had follow-up visits. At T0, serum CRP concentration was above the reference interval in 73.1% (49/67), and was within the reference interval (0-141.9 nmol/L) throughout hospitalization in only 6% (4/67). Serum CRP concentrations were significantly higher (P < 0.0001) at T0 (882.9 ± 1082.9 nmol/L) and at all time points during hospitalization (P < 0.0001) compared to T1m, with highest concentrations observed at T24 (906. 7 ± 859.0 nmol/L). At T1m, serum CRP concentrations were within the reference interval (22.9 ± 42.9 nmol/L) in 95% (18/19) of dogs. Logarithmic concentrations of serum CRP and plasma IL-6 were significantly correlated (P < 0.001, r = 0.479). None of the measured cytokines were associated with disease category or outcome. Conclusions -Serum CRP concentration is increased in dogs with SIRS, and decreases during treatment and hospitalization. Serum CRP, plasma IL-6, and plasma TNF-␣ concentrations cannot predict outcome in dogs with SIRS.