Generally, mineral processing plants generate a large quantity of waste in the form of fine particles. The flotation speed of mineral microbubbles by coarse bubbles is dramatically higher than that of individual particles. The advantage of microbubbles is due to the increase of binding efficiency of conventional bubbles with fine particles coated with microbubbles. Here, the focus is on reducing chemicals consumption and improving recovery. After preparing a representative sample, XRF, XRD, and mineralogical analyses were performed. Then 50 experiments were selected by experimental design using the response surface method (RSM), and in the form of central Composite design (CCD) by (design expert) DX 13 software. The interactions of collector consumption, frother agent, pH, particle size, and solid percentage were investigated, and 25 experiments using typical flotation and without nano-microbubbles and others with nano-microbubbles were conducted. The laboratory standard limit of the collector used in the pilot plant of the Sarcheshmeh Copper copper complex is 40 g/t (25 g/t of C7240 plus 15 g/t of Z11). Here, by consuming 20 g/t of collector in the absence of nanomicrobubbles, a recovery of 79.96% and in the presence of nanomicrobubbles, a recovery of 80.07% was obtained, that is a 50% reduction in collector consumption and a 0.11% increase in recovery was observed. Also the laboratory standard limit of frother used in the pilot plant of Sarcheshemeh Copper Complex is 30 g/t (15 g/t of MIBC plus 15 g/t of A65). Here, by using 10 g/t of frother in the absence of nanomicrobubbles, a recovery of 78.12%, and in the presence of nanomicrobubbles, a recovery of 82.05% was obtained. In other words, a decrease of 66.6% in the consumption of frother and an increase of 1.93% in recovery was observed.