PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) represents a potential clinical tool in treating bipolar disorder (BD). However, the intervention of rTMS combined with pharmacotherapy on the plasma fatty acids (FAs) in patients with bipolar depression has not been reported yet. METHOD: In this study, we assessed the clinical symptoms and evaluated plasma FAs from 30 inpatients with bipolar depression at baseline phase (BD group), after 2 weeks of treatment with rTMS combined with quetiapine and mood stabilizer (BD-2w group), and 32 healthy controls (HCs). FINDING: We found that acetic acid, propionic acid, isovaleric acid, isobutyric acid, and valeric acid, as well as levels of total short-chain fatty acids (SCFAs), were decreased in both BD and BD-2w groups, and levels of several medium- and long-chain fatty acids (MLCFAs) were altered in BD when compared with HC. Moreover, 2 weeks of treatment increased the levels of various MLCFAs. Finally, we developed combinational FAs panels that could distinguish BD from HC (area under the curve [AUC] = 0.961), BD-2w from HC (AUC = 0.978), and BD from BD-2w (AUC = 0.891) effectively. CONCLUSION: These findings might provide a basis for developing diagnostic methods and reveal the potential relationship between bipolar depression and plasma FAs.