Low-dose macrolides (LDM) are anti-inflammatory agents with antineutrophilic activity, but patient selection for LDM therapy in treating chronic rhinosinusitis (CRS) is controversial. This study aimed to assess factors which predict LDM responders. A prospective cohort study was performed. Patients with CRS received roxithromycin (150 mg) once daily for 12 weeks. Nasal secretions and serology were collected. Nine predictors for LDM response were assessed: nasal secretion IgE, nasal secretion IL-5, serum IgE, serum eosinophils, serum neutrophils, nasal polyps, asthma, allergy, and aspirin hypersensitivity, using receiver-operating curve analysis and multivariable logistic regression. Macrolide responders were those with sino-nasal outcome test-22 improvement, symptoms visual analogue scale decreased to ≤ ≤ ≤5, and no rescue medication. One hundred CRS patients (mean age 47.4 +- 14.1 years, 45% male) were enrolled. Univariable logistic regression showed local total IgE less than 5.21; and serum eosinophils less than 2.2% associated with macrolide response. Multivariate models showed local total IgE maintained an independent association with macrolide response, with an ability to discriminate between responders and non-responders of 63%. Serum total IgE, nasal secretion IL-5, serum neutrophil, nasal polyp, asthma, allergy, and aspirin hypersensitivity showed no association with LDM response. Low total IgE level in the nasal secretion but not in the serum, predict LDM response.