Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays essential roles in lipids and lipoprotein metabolism. High levels of PCSK9 are associated with hyperlipidemia. Vitamin B12 deficiency and increased levels of Homocysteine were also found to be associated with hyperlipidemia. This study aims at investigating the relationship of PCSK9 with homocysteine and vitamin B12 in hyperlipidemic subjects. Methods: The study comprised a total of 90 subjects; 47 hyperlipidemic and 43 normolipidemic. Lipid profile (total cholesterol, LDL-C, HDL-C, and triglycerides), homocysteine, vitamin B12 and PCSK9 were determined using conventional laboratory procedures. Results: As expected, total-and LDL-cholesterol in hyperlipidemics were higher than in normolipidemics. No differences in HDL-C and triglyceride were observed. PCSK9 levels were higher in hyperlipidemics as compared to normolipidemics (2011 ± 648 pg/mL vs 1762 ± 384 pg/mL, p value < 0.05, respectively). No significant differences in vitamin B12 and homocysteine were observed. The concentrations of PCSK9 were higher in hyperlipidemic subjects taking statins as compared to those not taking any (2135 ± 793 pg/mL vs 1840 ± 414 pg/mL). Total- and LDL-cholesterol showed significantly positive correlation with PCSK9 (r = 0.281 and 0.378, p value < 0.05, respectively). Significant positive correlation was also observed between LDLcholesterol and PCSK9 for subjects on statins (r = 0.378). No correlation observed in those not taking statins. On the contrary, LDL-cholesterol correlated negatively with vitamin B12 (r = –0.281, p <0.05), and correlated positively with homocysteine (r = 0.308, p < 0.05). A significant negative correlation was also observed between vitamin B12 and homocysteine (r = –0.304, p < 0.05). Additionally, a significant negative correlation between homocysteine and PCSK9 in hyperlipidemic subjects (r = –0.265, p < 0.05). Conclusions: This study showed that PCSK9 were elevated in hyperlipidemia and tends to be higher in hyperlipidemic subjects taking statins. The increased levels of PCSK9 along with increased homocysteine on one hand, and the decreased levels of vitamin B12 on the other, plays a role in increasing the levels of total- and LDLcholesterol.