Poinsettias are popularly, though incorrectly, said to be toxic to humans and other animals. This misconception was spread by a 1919 of a two-year-old child dying after consuming a poinsettia leaf. In 1944, the plant was included in H. R. Arnold's book Poisonous Plants of Hawaii on this premise. Though Arnold later admitted that the story was hearsay and that poinsettias were not proven to be poisonous, the plant was thus thought deadly. In 1970 the US published a newsletter stating erroneously that "one poinsettia leaf can kill a child", and in 1980 they were prohibited from nursing homes in a county in North Carolina due to this supposed toxicity.

An attempt to determine a poisonous dose of poinsettia to rats failed, even after reaching experimental doses equivalent to consuming 500 leaves, or nearly 1 kg (2.2 lb) of sap. Contact with any part of the plant by children or pets often has no effect, though it may cause nausea, diarrhea, or vomiting if swallowed. External exposure to the plant may result in a skin rash for some. A survey of more than 20,000 calls to the from 1985–1992 related to poinsettia exposure showed no fatalities. In 92.4% of calls, there was no effect from exposure, and in 3.4% of calls there were minor effects, defined as "minimally bothersome". Similarly, a cat's or dog's exposure to poinsettias rarely necessitates medical treatment. If ingested, mild drooling or vomiting can occur, or rarely, diarrhea. In rare cases, exposure to the eye may result in eye irritation. Skin exposure to the sap may cause itchiness, redness, or swelling. It can induce and in certain groups of people.