The fruit bodies of A. sphaerobulbosa are damaging to the liver; the toxicity is thought to be largely due to a rare amino acid.

Although not considered as toxic as its deadly relatives (e.g. the death cap and the destroying angel), A. sphaerobulbosa is thought to have caused fatalities.

A minimum single lethal dose of mushroom extract (equivalent to 4.5 grams of fruiting body per kilogram of mouse body weight) caused mice to become prostrate 6 hours after injection; shortly after the mice had diarrhea, then ultimately died between 24 and 48 hours after administration of the extract.

Although not as toxic as the destroying angel (A. virosa) or the death cap (A. phalloides), A. sphaerobulbosa causes changes in liver function similar to these species.

Effects include a decrease in blood sugar levels, depletion of stored carbohydrate reserves (liver glycogen), and an increase in transaminases.