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Electroacupuncture (EA) has been clinically used to treat depression and has resulted in favorable effects in China. However, results from animal studies and pathology do not reflect the influence of electroacupuncture treatment on in vivo physiological functions. To thoroughly and dynamically observe pathological changes during depression, the present study established EA + fluoxetine and fluoxetine groups to observe depression in patients. 1H-magnetic resonance spectroscopy was utilized to determine the correlation between hippocampal frontal lobe metabolite changes and mental disorder scale. Results revealed significantly increased N-acetylaspartate (NAA)/creatine (Cr) in the bilateral hippocampus and right frontal lobe of depression patients treated with EA compared with fluoxetine. Changes in NAA/Cr in bilateral hippocampus and right frontal lobe in both groups, before and after treatment, negatively correlated with severity and curative effects. Choline/Cr changes in the bilateral frontal lobes of both groups were significant before and after treatment, but negatively correlated with curative effects. Choline/Cr changes in the bilateral hippocampus were significant in the EA + fluoxetine group before and after treatment, but negatively correlated with severity and the curative effects of depression. These results demonstrate abnormal biochemical metabolism in bilateral frontal lobes and hippocampus of depression patients, and show that EA significantly altered biochemical indices in the frontal lobes and hippocampus compared with fluoxetine.