Background: There is a shortage of blood in the blood banks due to limited donation. By and rnlarge, it is widely believed that blood donation has multiple health benefits. However, there are rnlimited studies that support health benefits; As a result, assessing the lipid profile and rnhematologic parameters of the regular blood donors is an indispensable to evaluate an rnindividualâ€™s risk for chronic inflammation. rnObjective: We strived to compare lipid and haematological profiles of the regular and first-rntime blood donors in the National Blood Bank Service of Ethiopia. rnMaterials and Methods: This comparative cross-sectional study was involved 104 samples rn(52 each of regular and first-time donors). Anthropometric parameters of donors measured and rnBlood was drawn from each participants for hematologic and lipid profile determination. Data rnwere analyzed using SPSS version 21, Chi-square (Ï‡Â²) was used to compare the relationship rnbetween categorical variables and independent t-test was used to compare the mean of the two rngroups. A p-value < 0.05 was considered statistically significant. rnResults: The mean total cholesterol, LDL-c, LDL-c/HDL-c and TC/HDL-c ratios were rnsignificantly lower in the regular blood donors than the first-time donors. Even though the level rnof HDL-c was higher in regular blood donors compared to first-time blood donors, it was not rnstatistically significant. The mean of some hematologic parameters like a platelet, RDW, rnlymphocyte, and MCH were significantly lower in regular blood donors than first-time blood rndonors. BMI and WHR in regular donor were less than the first time donors, albeit statistically rninsignificant. rnConclusions: Interestingly, blood donation has a significant health benefit by lowering TC,rnTG and LDL-c that have a potential risk for developing chronic inflammation.