The dilution effect of high plasma volume contributes to a lower level of specific tumor marker such as prostate-specific antigen. To date, few studies have focused on this effect of other tumor marker levels. Therefore, we evaluated the dilution effects of a higher plasma volume on lowering the serum concentration of various tumor markers such as CA125 and CA19-9. Data from patients (age >= 40 years) visiting our public health center between March 2007 and March 2013 were gathered. A total of 19,439 male and 11,655 female native Koreans were eligible to have a serum CA125 and CA19-9 screening for ovarian and pancreatic cancer, respectively. CA125 levels in 11,234 women were analyzed. There was a statistically significant trend toward a lower likelihood of having a serum CA125 level >35 U/mL with increased body mass index (BMI), with obese men having a 53.1% lower likelihood than those with a normal BMI. After CA19-9 analysis in 29,978 participants, there was also a significant trend toward a lower likelihood of having a serum CA19-9 level >35 U/mL with increased BMI, with obese men having a 27.0% and obese women having a 32.7% lower likelihood than those with a normal BMI. These results might affect tumor screening efficiency for ovarian and pancreatic cancer using serum CA125 and CA19-9, respectively. Further studies are needed to better define these results in clinical practice.