The nutrients-rich aquaculture effluent may cause severe environmental and ecological destructions if discharged without adequate treatment. Microalgae can serve as a good candidate in aquaculture effluent polishing since it can realize water purification as well as in situ resource transformation as aquaculture feeds comparing to traditional remediation efforts. Enhanced nutrients removal by nutrients deprived microalgae has been revealed before, but repetitive nutrients deprivation is so far applied only for biofuel production purposes, and it is still unclear whether such a strategy can be adopted for further effluent polishing. This study comprehensively investigated the improved aquaculture effluent polishing by once and repetitive nutrients deprivation of indigenous seawater Chlorella sp. Synthetic effluent of various strengths (total nitrogen = 2–50 mg/L, total phosphorus = 0.2–5 mg/L) were first treated by nutrients replete microalgae, then subsequently polished by nutrients deprived microalgae. A semi-continuous sequential system was established and evaluated at various dilution plans, using both nutrients replete and repetitive nutrients deprived microalgae. Results showed that nutrients replete microalgae could only polish low strength aquaculture effluent to discharge acceptable levels (dissolved inorganic nitrogen≤0.5 mg/L, phosphate≤0.05 mg/L), while a following treatment by nutrients deprived microalgae could also treat moderate strength effluent to meet the discharge limits, and the improved nutrients removal was most efficient (>90% removal) during the first two days of effluent polishing. The semi-continuous sequential system with repetitive nutrients deprivation at two-day intervals could polish the high strength effluent to discharge acceptable levels respectively after 5, 7, and 9 days, using 1, 2, and 3 days of water exchange intervals in each circulation treatment. The extra microalgal biomass produced during repetitive nutrients deprivation (0.28–0.8 g/L biomass increase during each round of deprivation) was advantageous for system scale-up, or could be utilized as in situ aquaculture feed or other value-added products due to its lipid and carbohydrate rich properties.