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In hard times of supply shortages, starvation was a major struggle for the travelers. Desperate and starving people would cut meat out from rotting carcasses just for food. Some desperately even resorted to cannibalism and ate their friends and family who had recently died. Even more people boiled hides and ate them to feed their families. Starvation and malnutrition was one of the biggest factors on the Oregon Trail.

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The death of friends and family, and sometimes strangers greatly affected the morale of travelers on The Oregon Trail. At the time in the 1840's the advancement of medicines had not yet been discovered yet and when people got sick or injured, death was much more likely to be the result than it would be today. The sight of travelers dying on The Oregon Trail greatly reduced morale of travelers because they didn't know if it was going to be them dying next.

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The leading cause of death by accidents was from people falling or slipping and getting run over by a wagon wheel. The second leading cause was by firearms. Accidental discharging of firearms was common and killed a large number of pioneers. Another common accident was being trampled by stampeding cattle and livestock.

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Diseases such as cholera, small pox, flu, measles, mumps, tuberculosis, and other illnesses could spread through wagon trains and camps quickly. Such diseases could infect a person early in the morning and they could be dead by noon if they were sick enough.

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Crossing rivers was one of the most dangerous things pioneers had to do. Swollen rivers could tip over and drown people and their horses and oxen. Accidents that occur when crossing rivers sometimes resulted in death, wagons tipping, and losing valuable supplies.

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Natives were sometimes friendly and helpful to travelers but they were always a threat to the emigrants and there was always the threat of being attacked. Typically Natives only attacked when their land was crossed or if there was a dispute but travelers usually avoided contact with them if possible .

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Travelers after traveling for approximately three months would have to begin crossing the Rocky Mountains and then soon after the Blue Mountains. To get their wagons up the mountains they had to use pulleys to haul it and large rocks to prevent it from rolling and on the way down the other side they had to get it downhill at a safe speed. Rivers, trails, and topography were other terrain factors that greatly affected the travelers.

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In the event that travelers did not bring the amount of supplies they needed to bring or if they did not have enough room for all of their supplies, they would have to resort to rationing food, hunting and scavenging, and taking the risk of death if their wagons happen to break down.

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Common causes of injury and death came from natural events such as lighting, hailstorms, grass fires, snakebites, and sometimes suicide.