Background Premarital screening is fast gaining ground as a prerequisite for the solemnization of holy matrimony by many faith-based organizations in Nigeria, yet there is no literature on the subject in Yenagoa, Bayelsa State. Methods One hundred and five (105) premarital heterosexual couples (105 males and105 females) were screened for the presence of human immunodeficiency virus (HIV), haemoglobin genotypes, and ABO and Rhesus blood groups using standard laboratory procedures. Results The prevalence of HIV in this study was found to be 1.0%. The frequencies of the HbAA (74%), HbAS (24%), HbAC (1.5%), HbSS(0.5%) while that of ABO and Rh blood groups were: group A (21%), B (25%), AB (6.0%), 0 (48%), Rh ‘D’ positive (97%) and Rh ‘D’ negative (3.0%). The distribution of these variables between the sexes was statistically significant (χ2=25.68, p<0.01). The frequencies of the haemoglobin genotype combinations of the intending couples were as follows: HbAA/AA (55%), AA/AS (33%), AS/AS (8.0%), AA/AC (2.0%), AS/AC(1.0%) and AS/SS (1.0%) . This distribution pattern was also found to be highly statistically significant (χ 2 = 24.459, p < 0.0001). The mean age of the participants was 31.91 ± 4.80years for male and 26.105 ± 4.29 years for female (t = 3.272, p < 0.05). Conclusion This study observed a low prevalence of HIV among the premarital couples and a relatively high frequency of HbAS/AS couples. The ABO and Rh blood groups were found to be stable and consistent with previous reports. For the prevention of hereditary blood diseases, haemolytic disease of the newborn and transmission of HIV to offspring, premarital testing should be encouraged. Keywords: Human immunodeficiency Virus(HIV), Haemoglobin Genotype, ABO And Rhesus Blood Group