Background: Recent studies suggest that in sub-Saharan African, a large proportion of new HIVrninfections occur within sero-discordant couples and in countries with generalized HIV epidemicsrnincluding Ethiopia sero-discordant relationships are common. Thus, it remains to be a majorrnchallenge to achieve the full impact of HIV/AIDS intervention. rnObjective: To assess the magnitude of HIV sero-discordance and its associated factors amongrncouples tested in Zewditu Memorial Hospital, Addis Ababa, Ethiopia.rnMethods: Cross-sectional chart review for a total of 13,423 couples from January 2005 tornDecember 2012 was conducted. Quantitative and qualitative data analyses were done to assessrnthe magnitude and its associated factors with HIV sero-discordance among couples. To rnsupplement the quantitative data in-depth interview was conducted in 4 sero-discordant couples rnand 3 VCT counselors. Data were entered using Epi-info version 3.5.3 and quantitative data wasrnanalyzed using SPSS for windows version 19 software. Qualitative data was transcribed based onrnthe objectives of the study and the results were described in narratives using well-said verbatim.rnResults: Among a total of 13,423 HIV tested couples 886 of them were HIV sero-discordant andrnthe magnitude of sero-discordance was found to be 6.6%. Sero-discordance was more prevalentrnamong married and widowed couples counting 20% and 16.4% respectively. Secondaryrneducation (AOR= 2.42; 95% CI: 1.527, 3.83); tertiary level (AOR=1.60; 95 % CI: 1.008, 2.54);rnable to read and write (AOR=2.68; 95% CI: 1.63,4.39); condom not used regularly in the last 3rnmonths (AOR=2.145; 95% CI: 1.625, 2.831); suspected exposure within 4 to 6 monthsrn(AOR=2.31; 95% CI: 1.53, 3.50); suspected time over 6 months (AOR=1.98; 95% CI: 1.409,rn2.79); employed (AOR=1.26; 95% CI: 1.03, 1.54); unskilled occupation (AOR= 1.851; 95% CI:rn1.152, 2.975); housewife (AOR= 0.533; 95% CI: 0.38, 0.75); history of STI (AOR= 0.745; 95%rnCI: 0.56, 0.99) were statistically significant with HIV sero-discordance.rnConclusion and Recommendation: Substantial prevalence of sero-discordance was observedrnamong married couples. Sero-discordant couples occupied with handful misconception and theyrnare ambivalent for decision making. Sero-discordant result among couples is still mysterious; asrna result, justify it from spiritual point of view and face many challenges and dilemmas. Intensivernefforts should be made to encourage married couples aware of their own and their partnersâ€™ serostatus.rnEmpoweringrnandrneducatingrncommunityrnandrnongoingrncounselingrnisrnrecommended.