Abstract Introduction The role of obesity in female sexuality is controversial and there are no intervention studies aimed at evaluating the effect of the Very Low Calories Ketogenic Diet (VLCKD) on female sexual function, in particular on arousal. Objective To evaluate the psychosexual correlates of obesity and Metabolic Syndrome (MetS) in a sample of women consulting for sexual symptoms; to investigate the change in measures of arousal after weight loss obtained with VLCKD. Methods In a retrospective study, n=322 women consulting for sexual symptoms were enrolled. The patients underwent a clinical, laboratory, sexual and psychological examination and were studied by color-Doppler ultrasound for the evaluation of genital vascularization, with measurement of the Pulsatility Index (PI) of the clitoral artery. They completed the Female Sexual Function Index (FSFI), Female Sexual Distress Scale - Revised (FSDS-R), Body Uneasiness Test, Eating Disorder Examination Questionnaire (EDE Q), and Middlesex Hospital Questionnaire, for psychiatric symptoms. Twelve patients underwent a nutritional intervention aimed at weight loss, based on a VLCKD protocol. These cases were compared with patients treated with different strategies for sexual symptoms, in a 1:1 case-control study (matched for BMI, age and menopausal status). Results In the total sample, clitoral PI was significantly higher in obese women (p = 0.018) and in those diagnosed with MetS (p=0.043). A statistically significant inverse correlation emerged between WC ≥ 88 cm and FSFI Arousal score (p=0.028). In patients undergoing a nutritional intervention with VCLKD protocol (n=12), after a mean follow-up of 20+-2 weeks, BMI showed a reduction of 6.7+-2.8 kg/m2 (p<0.001) and WC of 14.3+-5.2 cm (p<0.001), with fat mass loss of 14.6+-5.4 kg (-37.1%; p<0.001). At follow-up, the total FSFI and FSDS-R scores significantly improved (17.0+-13.6 vs. 11.2+-7.9, p=0.016, and 7.4+-8.3 vs. 13.3+-10.6, p=0.039, respectively). Among the FSFI subdomains, Arousal showed a significant increase (p=0.035). We also observed an improvement in EDE total score (p=0.032), Shape (p=0.008) and Weight subscales (p=0.011), BUT-B Positive Symptoms Distress Index (p=0.009) and BUT-A Body Image Concerns (p=0.043), and MHQ total score (p<0.001). The clitoral artery PI at follow-up showed a non-significant reduction. At multivariate analysis, the change in the Total FSFI was correlated with the BUT-B PSDI score change (p=0.031) and the EDE Shape change (p=0.043), when including DeltaMHQ and DeltaWC as further covariates. Finally, in a 1:1 case-control study, a significant difference emerged in the improvement of FSFI total score, which was more relevant in cases than in controls (p=0.046); on the other hand, there was no difference in the change in FSDS-R score between cases and controls. Conclusions Our data suggest that weight loss obtained by VLCKD is associated with an improvement in sexual function, and in particular in Arousal, whose change could be mediated by improved body image parameters. The effect of weight loss on cardiometabolic risk factors related to sexual dysfunction requires dedicated longitudinal studies, with the use of objective methods. Disclosure No