Ethosuximide, sold under the brand name Zarontin among others, is a medication used to treat absence seizures. It may be used by itself or with other antiseizure medications such as valproic acid. Ethosuximide is taken by mouth.

Ethosuximide is usually well tolerated. Common side effects include loss of appetite, abdominal pain, diarrhea, and feeling tired. Serious side effects include suicidal thoughts, low blood cell levels, and lupus erythematosus. It is unclear if it has adverse effects on the fetus during pregnancy. Ethosuximide is in the succinimide family of medications. Its mechanism of action is thought to be due to antagonism of the postsynaptic T-type voltage-gated calcium channel.

Ethosuximide was approved for medical use in the United States in 1960. It is on the World Health Organization's List of Essential Medicines. Ethosuximide is available as a generic medication. As of 2019^[update], its availability was limited in many countries, with concerns about price fixing in the United States.

Ethosuximide is approved for absence seizures, and is considered the first choice medication for treating them, in part because it lacks the idiosyncratic hepatotoxicity of the alternative anti-absence drug, valproic acid.

As with other anticonvulsants, ethosuximide carries a warning about use during pregnancy. Although a causal relationship with birth defects has not be established, the potential for harm to the baby is weighed against the known harm caused by a mother having even minor seizures.

The following can occur with or without bone marrow loss:

Valproates can either decrease or increase the levels of ethosuximide; however, combinations of valproates and ethosuximide had a greater protective index than either drug alone.

It may elevate serum phenytoin levels.