Background The presence of small dense LDL is associated with obesity and type 2 diabetes and an increased risk for cardiovascular disease. Apolipoprotein C-III (apoC-III) is involved in the formation of small dense LDL, but the exact mechanisms are still not well defined. ApoC-III is a glycosylated apolipoprotein, with three major glycoforms: apoC-III0, apoC-III1, and apoC-III2 that contain zero, one, or two molecules of sialic acid, respectively. In our previous work, we reported an association among apoC-III0 and apoC-III1, but not apoC-III2 with fasting plasma triglyceride levels in obesity and type 2 diabetes. Objective The goal of this study was to determine the relationship between changes in the major apoC-III glycoforms and small dense LDL levels after dietary interventions. Methods Mass spectrometric immunoassay (MSIA) was performed on fasting plasma samples from 61 subjects who underwent either a high carbohydrate diet (n=34) or a weight loss intervention (n=27). Results After both dietary interventions, changes in total apoC-III concentrations were associated with changes in LDL peak particle diameter (r= −0.58, p<0.0001). Increases in total apoC-III concentrations following the high carbohydrate diet were associated with decreases in LDL size (r= −0.53, p=0.001), and decreases in apoC-III concentrations following weight loss were associated with increases in LDL peak particle diameter (r= −0.54, p=0.004). Changes in concentrations of apoC-III1 and apoC-III0, but not apoC-III2, were associated with changes in LDL peak particle diameter in both the weight loss and high carbohydrate interventions. Conclusion We conclude that apoC-III0 and apoC-III1, but not apoC-III2 are associated with the formation of small dense LDL.