Nutrient runoff and hypoxia are significant environmental challenges facing the Mississippi River.

Excessive nutrient runoff, particularly from agricultural fertilizers, enters the river and travels downstream into the Gulf of Mexico. This influx of nutrients, primarily nitrogen and phosphorus, promotes the growth of algae in the water, leading to hypoxia, or low oxygen levels. The resulting "dead zone" in the Gulf of Mexico creates conditions that are harmful to marine life, including fish and shellfish. This is a major ecological concern, as it disrupts the health of aquatic ecosystems and fisheries, affecting both the river's biodiversity and the surrounding economy.