The objective of this study was to evaluate the effect of irrigation frequencies and substrate volumes on fruit mass, fruit quality and water use efficiency of cantaloupe melon in protected environment. The study was conducted at the Federal University of Rondonópolis, MT, Brazil, from February to August 2021, in randomized block design in a 3 × 4 factorial scheme with four replicates. The substrate volumes used in plastic pots were 5, 10 and 15 dm3 and the irrigation frequencies were once a day, twice a day, three times a day and once every other day. The characteristics evaluated were fruit mass, pulp thickness, water use efficiency, soluble solids content, and titratable acidity. The irrigation frequencies of once and three times a day showed the best performance for fruit mass and pulp thickness. The water use efficiency was higher for the frequency of three times a day. With the exception of titratable acidity, the substrate volumes of 10 and 15 dm3 showed the highest performances for all the variables evaluated. As for the soluble solids content, all fruits showed levels that classified them as extra fruits, of high quality and indicated for exportation.