Background The relationship between serum vitamin C (sVC) and blood lipids in adolescents in the US has not been thoroughly studied. This study investigates the correlation between sVC and blood lipids among adolescents using data from the National Health and Nutrition Examination Survey (NHANES). Methods Data from the NHANES 2003-2006 and 2017-2018 cycles, encompassing 4,965 participants aged 12-19 years, were analyzed. sVC served as the independent variable and blood lipids as the dependent variables. Multiple linear regression models assessed the relationship between sVC and blood lipids, with subgroup analyses based on sex, age, and race. Additionally, smooth curve fitting and saturation threshold analysis were employed to explore nonlinear relationships. Results Adjusted analyses revealed a positive correlation between sVC and high-density lipoprotein cholesterol (HDL-C) (beta = 2.77, 95%CI 2.06-3.47), with no significant association with total cholesterol, low-density lipoprotein cholesterol (LDL-C), or triglycerides. This positive correlation persisted across subgroups divided by age, gender, and race (p < 0.05). The nonlinear relationship between sVC and HDL-C was characterized by an inverted U-shaped curve in adolescents aged 12-15 years, males, females, and non-Hispanic Whites. Conclusions This study confirms a positive association between sVC levels and HDL-C in adolescents, suggesting that higher vitamin C intake/status may be associated with a higher HDL-C in adolescents.