SummaryBackgroundInnate immunity has been thought to be involved in asthma pathogenesis. Pentraxins, acting as soluble pattern recognition molecules, play an important role in humoral innate immunity. Asthma is a heterogeneous inflammatory disease of airways and can be classified as eosinophilic or non‐eosinophilic asthma.ObjectiveTo investigate whether pentraxin levels differ in subjects with eosinophilic versus non‐eosinophilic asthma. Furthermore, to access the predictive performance of pentraxin levels for discriminating asthma inflammatory phenotypes.MethodsA total of 80 asthmatic patients and 24 healthy control subjects underwent sputum induction at study inclusion. Differential leucocyte counts were performed on selected sputum. Plasma C‐reactive protein (CRP), serum amyloid P (SAP), pentraxin 3 (PTX3), and sputum SAP, PTX3, IL‐8 levels were determined by enzyme‐linked immunosorbent assay.ResultsSubjects with non‐eosinophilic asthma had significantly increased pentraxin levels compared with those with eosinophilic asthma and healthy controls, with median (interquartile range) plasma CRP levels of 0.86 (0.28‐2.07), 0.26 (0.14‐0.85), and 0.15 (0.09‐0.45)mg/L (P < .001), respectively, plasma SAP levels of 33.69 (19.79‐58.39), 19.76 (16.11‐30.58), and 20.06 (15.68‐31.11)mg/L (P = .003), respectively, and sputum PTX3 levels of 4.9 (1.35‐18.72), 0.87 (0.30‐2.07), and 1.08 (0.31‐4.32)ng/mL (P < .001), respectively. Conversely, sputum SAP concentrations of eosinophilic asthmatics (median, 21.49 ng/mL; IQR, 6.86‐38.79 ng/mL) were significantly higher than those of non‐eosinophilic patients (median, 8.15 ng/mL; IQR, 2.82‐18.01 ng/mL) and healthy controls (median, 8.79 ng/mL; IQR, 2.00‐16.18 ng/mL). Asthma patients with high plasma CRP (P = .004), SAP (P = .005) and sputum PTX3 levels (P < 0.001) also had significantly lower sputum eosinophil percentages. Sputum PTX3 levels had the best power (11.18‐fold, P < .001) to predict non‐eosinophilic airway inflammation in asthma patients.Conclusion and Clinical RelevancePentraxin levels differed significantly between patients with non‐eosinophilic asthma and those with eosinophilic asthma. Furthermore, elevated pentraxin expressions may predict non‐eosinophilic airway inflammation in asthmatic patients.