Objective The relationship between RBC indices and metabolic diseases remains unclear. The association between anemia and obesity is also controversial. The present study aimed to investigate the relationship between RBC indices and metabolic diseases caused by obesity and evaluate the effect of body mass index (BMI) on RBC indices on the Ravansar cohort data. Method For the purpose of this study, 9826 participants aged 35–65 years (5158 females and 4668 males) were recruited in the analyses. A quadratic prediction fit plot investigated the association between RBC indices with BMI and lipid profile. The odds ratio of obesity-related diseases in each quartile category of RBC indices and anemia was estimated using multivariable logistic regression models. Results Subjects in the fourth quartiles of RBC count, hematocrit (HCT), hemoglobin (HGB), and red cell distribution width (RDW) had a higher risk for obesity-related diseases compared to the first quartiles. However, individuals with the mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) in fourth quartiles had lower ORs of obesity-related diseases. While BMI reduced the effect of RBC count, HCT, HGB, and RDW on the incidence risk of obesity-related disease, it increased the impact of MCV, MCH, and MCHC. There was a negative association between BMI and RBC indices except for RDW. The BMI effect on RBC indices was different in normal and obese individuals. BMI in mild anemia lowered the risk of metabolic diseases, but it increased the risk of metabolic diseases for moderate anemia. Conclusion A higher risk of obesity-related diseases was observed in the fourth quartiles of RBC count, HCT, HGB, and RDW compared to the first quartiles. However, the incidence risk was lower for MCV, MCH, and MCHC. BMI plays an anemia-type dependent role in the relationship. Consideration should be given to the type of anemia in the relationship between BMI and anemia.