Background Vegetarian diets adapted for various reasons that may include religious, ethical, and health considerations have reasonable health benefits including weight loss, and favorable metabolic changes. However, studies that assessed health benefits associated with vegan diet practices during the Ethiopian Orthodox Christian (EOC) Lenten fasting remains limited. This study has, therefore, assessed how short-term vegan diet associated with metabolic traits, including weight, body mass index (BMI), circumference, blood pressure, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), through longitudinal cross-sectional study design. Methods Seventy-five subjects (34 females and 41 males) with a mean age of [+SD] 27.3 + 5.8 years (range, 18 and 35) took part in the study. The study followed three assessment sessions: at baseline, during the Lenten (week 7), and 7 weeks after the end of the Lenten (week 14). An automatic chemistry analyzer (Mindray, BE-2000, China) used for lipid profile analysis. We used paired sample t-test in pre and post-performance and repeated measures ANOVA with Bonferroni post hoc adjustment between time points. The statistical significance was set at p < 0.05. Results The EOC fasting with vegan diet induced significantly lower blood pressure, weight, BMI, TC, HDL-C, LDL-C, and TC: HDL-C ratios, during Lenten (that is vegan diet consumption), but a regain noted in these parameters 7-weeks after Lenten (that is omnivore diet). On gender differences, vegan diet associated with significantly lower blood pressure, TC, and LDL-C in females compared with age-matched male counterparts. Some methodological limitations of this study are discussed with particular reference to lack of a randomized control