The effects of low-dose macrolide (LDM) therapy on pediatric chronic rhinosinusitis (CRS) patients are unknown. This study aimed to assess the effectiveness of LDM for treating pediatric refractory CRS. A retrospective study was conducted by a medical chart review. Pediatric CRS patients (age <15 years) who received LDM after standard medical treatments failure between 2013 and 2019 were identified. The LDM treatments with any macrolide agents, doses, and regimens were included. Any co-interventions were allowed. Duration of the LDM therapy was ≥6 weeks. Outcomes were the total nasal symptoms by the visual analogue scale (TNS), presence of individual symptoms, physician-assessment nasal discharge and adverse events. Six patients (67% male, mean age 7±3.4 years) were assessed. All patients had failed to intranasal steroids and nasal saline irrigation but continued. The addition of LDM significantly improved TNS (mean difference ± standard deviation 5.83 ± 1.33; 95% confidence interval 4.44-7.23, p< 0.001). At the end of treatment, the numbers of patients with individual symptoms were decreased: nasal obstruction (100%-67%), rhinorrhea (83%-50%), hyposmia (50%-0%), cough (100%-33%), and physician-assessment thick mucoid discharge (33%-0%). No patients had facial pain. One patient reported mild tolerable nausea. Preliminary findings of this study showed some beneficial effects of LDM added to intranasal steroids and nasal saline irrigation in pediatric CRS after standard treatments failure. The beneficial effects included the improvements of the TNS and individual nasal symptoms and decrease in thick mucoid discharge.