Antimicrobial effects of CuSO₄ and Na₂SeO₃ have been reported in the literature. As common sources of Cu and Se for ruminants, we aimed to evaluate the effects of lipid-coat protection of CuSO₄ and Na₂SeO₃ on microbial fermentation in a dual-flow continuous culture system. We used 8 fermenters in a 4 × 4 duplicated Latin-square design with a 2 × 2 factorial arrangement of treatments (2 mineral sources × 2 protection levels). Treatments were: 1) unprotected Cu and Se, 2) protected Cu + unprotected Se, 3) protected Se + unprotected Cu, 4) protected Cu and Se. Main effects of protection of Cu, Se, and their interaction were tested. Fermenters were fed 106 g DM/d and all diets had the same nutrient composition (16% CP, 31% NDF, 29.5% starch, 1.6 MCal ENl/kg, 18 ppm Cu, and 0.4 ppm Se). Experimental period length was 10 d (7 d of adaptation and 3 d for sample collections). Daily pooled samples of effluents were analyzed for VFA, NH₃-N, soluble Cu and Se, ruminal true digestibility of nutrients, and flows (g/d) of total N, NH₃-N, non-ammonia N (NAN), bacterial N, dietary N, RDP-N supply and bacterial efficiency. Kinetics of pH, VFA, and NH₃-N was evaluated as repeated measures in samples collected daily at 0, 1, 2, 4, 6, and 8 h post morning feeding. Protection of Cu, Se, or their interaction did not affect pH and NH₃-N kinetics. Protection of Se tended to reduce: NH₃-N effluent concentration (P = 0.09), NH₃-N flow (P = 0.07), and RDP-supply (P = 0.06); and tended to increase flows of: NAN (P = 0.06) and dietary N (P = 0.06). For VFA kinetics, protection of Cu reduced acetate % (P = 0.02), increased butyrate % (P = 0.04), and tended to decrease acetate:propionate (P = 0.06). Protecting both Cu and Se reduced isovalerate % (P = 0.05) and tended to reduce BCVFA % (P = 0.07). Our results suggest that lipid-coat protection of CuSO₄ and Na₂SeO₃ might benefit ruminal fermentation through increased efficiency of VFA synthesis and N utilization, respectively.