Abstract Background Brachycephalic obstructive airway syndrome (BOAS) results from upper airway anatomical abnormalities and may cause systemic effects depending on severity. Methods A prospective, case‒control and observational study was conducted. All dogs underwent a physical examination, BOAS functional grading, and venous and arterial blood sampling for haematological, biochemical, arterial blood gas and acute phase protein (APP) analyses. The hypothesis was that APPs, leukogram parameters and arterial blood gas alterations are associated with BOAS severity. Results Fifty‐two brachycephalic dogs were assigned to BOAS grades 0 ( n = 14), 1 ( n = 15), 2 ( n = 11) and 3 ( n = 12) and then compared with a mesocephalic group ( n = 15). BOAS grades 2 and 3 had higher haematocrit (HCT) ( p = 0.045), and all grades showed elevated leukocyte counts ( p = 0.005), creatinine ( p < 0.001), alpha‐1‐acid glycoprotein (AGP) ( p < 0.001), haptoglobin ( p = 0.036) and arterial pressure of carbon dioxide (PaCO 2 ) ( p < 0.001) compared to mesocephalic dogs. Total protein (TP) was higher in grades 1–3 ( p < 0.001), and albumin was lower in all BOAS grades ( p < 0.001). Lactate was elevated in grade 0 and controls ( p = 0.006). Multivariate analysis identified haemoglobin, HCT, TP, AGP, PaCO 2 , base excess and bicarbonate as the variables most strongly associated with BOAS severity. Limitations Age and weight selection criteria may have influenced BOAS scores and inflammatory markers. Conclusion BOAS grades were associated with hypoventilation, increased HCT and significant differences in inflammatory markers within physiological ranges, suggesting early systemic changes beyond respiratory dysfunction.