Obesity is linked to mitochondrial dysfunction. Mitokines are released in response to mitochondrial stress and the mitochondrial unfolded protein response. They play a crucial role in inter-organ communication. Bariatric surgery has been shown to improve mitochondrial dysfunction. In this study, we aimed to investigate the effects of obesity and bariatric surgery on mitokine levels. We prospectively recruited patients with morbid obesity (n = 45) and healthy controls (n = 35). Circulating mitokine levels—fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), and humanin—were measured using ELISA. In patients with obesity, mitokine levels were reassessed at 3 and 6 months following bariatric surgery. In obese patients, FGF21 and humanin levels were increased, while GDF15 levels were decreased compared to healthy controls (Figure 1). MOTS-c levels did not differ significantly between the two groups. When patients with obesity were stratified into two groups based on their respective baseline mitokine levels, GDF15 and humanin decreased at 3 months after bariatric surgery and remained unchanged at 6 months in the high baseline group. In the low baseline group, GDF15 decreased at 3 months after bariatric surgery but increased at 6 months. Obesity is associated with dysregulated circulating mitokine levels. Mitokine levels decrease early after bariatric surgery. This suggests that bariatric surgery could mitigate mitochondrial damage in patients with obesity.