Abstract: Tetracycline (TC) is extensively used in animal husbandry, aquaculture, and medical treatment. However, improper use or disposal of TC can increase its concentration in the aquatic environment. The effects of TC exposure on fish growth, oxidative stress, and lipid metabolism have been reported. But, the information on the potential and long-term effects on fish is very limited, especially at the environmentally relevant level. In this study, tilapia was used as an experimental model and exposed to three TC levels of 0 (control), 400, and 800 ng/L for 10 weeks. The results showed that, compared with the control, waterborne TC significantly improved growth performance, but increased triglyceride content and TC concentration in the liver. TC increased the expression of lipogenic genes (fas, scd, accα, srebp1, pparγ) and decreased the expression of lipolytic genes (atgl, hsl, cpt1 and pparα). In addition, these activities of 6-phosphogluconate dehydrogenase (6PGD), glucose 6-phosphate dehydrogenase (G6PD), isocitrate dehydrogenase (ICDH), malic enzyme (ME), and fatty acid synthase (FAS) increased significantly. but the activity of carnitine palmitoyltransferase 1 (CPT1) was significantly inhibited, parallel to gene expression. Moreover, waterborne TC significantly reduced the activities of catalase (CAT), total superoxide dismutase (T-SOD), and total antioxidant capacity (T-AOC), and induced oxidative stress in fish. The mitochondrial damage may be related to this and lead to a significant increase in malondialdehyde levels. Thus, the environmentally relevant TC concentration promoted growth performance, up-regulated lipogenic metabolism, reduced antioxidant capacity, and induced lipid peroxidation in GIFT tilapia.