The objectives of this study were to evaluate the influence of natural oil sands on the early developmental stages of white sucker (Catostomus commersoni) and to determine whether biochemical responses in this species were similar to native fish caught in the Athabasca Oil Sands area. Early life stage (ELS) sediment toxicity tests were conducted using controls, refer- ence sediments, natural oil sands, and industrially contaminated (wastewater pond) sediments collected from sites along the Athabasca River, Alberta (Canada). Eggs and larvae were observed for mortality, hatching, deformities, growth, and cytochrome P-4501A (CYP1A) activ- ity using immunohistochemistry. E-Nat-, S-Nat-, and wastewater pond sediment-exposed groups showed significant premature hatching, reduced growth, and exposure-dependent increases in ELS mortality and larval malformations relative to controls. The most common lar- val deformities included edemas (pericardial, yolk sac, and subepidermal), hemorrhages, and spinal defects. Juveniles exposed to oil sands and wastewater pond sediments (96 h) demon- strated significantly increased 7-ethoxyresorufin–O-deethylase (EROD) activity (30- to 50-fold) as compared to controls. Reference sediment-exposed groups and water controls demon- strated reliable embryo and larval survival, minimal malformations, and negligible CYP1A stain- ing. These observed signs of blue sac disease (ELS mortality, malformations, growth reductions, CYP1A activity induction) may produce deleterious reproductive effects in natural fish popula- tions exposed to oil sands mixtures.