The effects of micro-aeration and substrate selection on domestic sewage treatment performance were explored using three pairs (with or without micro-aeration) of horizontal subsurface flow (HSSF) constructed wetlands (CWs) filled with zeolite, ceramsite or quartz granules. The individual and combined effects of micro-aeration and substrate selection on the purification performance of the experimental-scale HSSF CWs were evaluated. The results showed that micro-aeration significantly increased the treatment efficiencies for chemical oxygen demand, total nitrogen, total phosphorus (TP), ortho-phosphate (PO4(3-)-P) and ammonium nitrogen (NH4+-N) using HSSF CWs, while the substrate selection significantly affected the TP, PO4(3-)-P and NH4+-N removal efficiencies (p<0.05). A two-way analysis of variance (ANOVA) indicated that there was a significant interaction term (i.e. micro-aeration×substrate selection) for NH4+-N removal (p<0.05). Among the three substrates, ceramsite was the best substrate for the treatment of domestic sewage using HSSF CWs. Therefore, the results of this study suggest that a ceramsite-filled HSSF CW with micro-aeration could be the optimal configuration for decentralized domestic sewage treatment.