Sertraline, sold under the brand name Zoloft among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. The efficacy of sertraline for depression is similar to that of other antidepressants, and the differences are mostly confined to side effects. Sertraline is better tolerated than the older tricyclic antidepressants, and it may work better than fluoxetine for some subtypes of depression. Sertraline is effective for panic disorder, social anxiety disorder, generalized anxiety disorder (GAD), and obsessive–compulsive disorder (OCD). However, for OCD, cognitive behavioral therapy, particularly in combination with sertraline, is a better treatment. Although approved for post-traumatic stress disorder (PTSD), sertraline leads to only modest improvement in this condition. Sertraline also alleviates the symptoms of premenstrual dysphoric disorder (PMDD) and can be used in sub-therapeutic doses or intermittently (luteal phase dosing) for its treatment.

Sertraline shares the common side effects and contraindications of other SSRIs, with high rates of diarrhea, nausea, insomnia, and sexual dysfunction, but it appears not to lead to much weight gain, and its effects on cognitive performance are mild. Similar to other antidepressants, the use of sertraline for depression may be associated with a mildly elevated rate of suicidal thoughts in people under the age of 25 years old. It should not be used together with MAO inhibitor medication: this combination may cause serotonin syndrome, which can be life-threatening in some cases. Sertraline taken during pregnancy is associated with an increase in congenital heart defects in newborns.

Sertraline was invented and developed by scientists at Pfizer and approved for medical use in the United States in 1991. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2016, sertraline was the most commonly prescribed psychotropic medication in the United States and in 2020, it was the twelfth most commonly prescribed medication overall in the United States, with over 38 million prescriptions.