Mannose binding lectin (MBL) plays an important role in innate immunity. Plasma MBL levels and MBL2 gene polymorphisms were studied in HIV-1 infected patients without tuberculosis (HIV+TB−) (n=151) and with tuberculosis (HIV+TB+) (n=109), HIV negative tuberculosis patients (HIV−TB+) (n=148) and healthy controls (n=146) by ELISA and genotyping by polymerase chain reaction based methods. MBL levels were significantly increased among HIV−TB+ and HIV+TB+ patients than controls and HIV+TB− patients (P<0.05). A significantly increased frequency of OO genotype of structural polymorphism and YY genotype of −221Y/X was observed among HIV−TB+ patients than controls. In HIV+TB+ patients, a significantly increased frequency of YA/YA diplotype (associated with very high MBL levels) was observed compared to controls (P=0.03). In HIV+TB+ patients, a significantly decreased frequency of medium MBL expression diplotypes (XA/XA and YA/YO) were noticed compared to HIV+TB− and healthy controls. The results suggest that YA/YA diplotype associated with very high MBL levels may predispose HIV-infected patients to tuberculosis while O/O genotype associated with very low MBL levels may be associated with susceptibility to tuberculosis in HIV uninfected individuals. Medium MBL expression diplotypes might protect against development of TB in HIV-infected patients.