The present study aimed to evaluate the effects of using different feeding regimes on the growth performance, economic efficiency, antioxidant status, and blood biochemical parameters of Nile tilapia, Oreochromis niloticus fingerlings for 10 weeks. Three hundred and sixty healthy fingerlings with average initial weight 16.9 ± 0.44 g were randomly allotted to 2×3 factorial design consisted of two feeding frequencies (once or twice a day) and three feeding intervals for each; regular feeding (daily feeding) or intermittent feeding; every other day (one day of feed one day of fasting) and every third day (one day feed two days fasting), respectively. The interaction occurred between feeding frequencies and intervals resulted in non-significant differences (P > .05) in the final body weight (BW) and body weight gain (BWG) between all experimental groups except for the group of fish fed once every third day that was lower than the group of fish fed twice daily (P < .05). However, the feed conversion ratio (FCR), protein efficiency ratio (PER), and protein productive value (PPV) were not influenced by the changes in the feeding frequency or interval. The daily feed intake was increased in intermittent feeding over daily feeding (P < .05). The expected weight gain for each daily feed intake was increased in fish fed twice every third day (P < .05). The dry matter content was increased (P < .01) in the fish fed twice daily. The crude protein content was decreased (P < .05) in the body of fish fed once every third day. The body fat content was decreased (P < .05) in fish fed twice every other day and fish fed every third day either once or twice. The body ash was increased (P < .05) in fish fed once every other day and twice every third day. The serum albumin was higher (P < .05) in fish fed once over those fed twice. The serum triglycerides level was increased (P < .05) in fish fed every third day compared to those regularly-fed. The serum level of glucose was higher (P < .05) in fish fed once every other day and twice every third day. Fish fed every third day had higher (P < .05) SOD activity than those regularly-fed. Mild to moderate alterations were observed in the histopathological examination of liver tissues from fish fed intermittently. The intestinal structure of fish regularly or intermittently-fed were within the normal range. Economically, intermittent feeding decreased the feed costs over regular feeding but the feed cost/kg gain was not affected (P < .05). It can be concluded that fish fasted and re-fed once or twice every other day and those that fasted and re-fed twice every third day can compensate for growth, while fish fasted and re-fed once every third day showed poor performance than regularly fed fish. Fasting can improve the antioxidant status of fish. However, intermittent feeding induced some degenerative changes in the histological structure of the liver.