Fish oil omega-3 fatty acids provide essential nutrients for brain health and functioning. These nutrients have been proven to be effective in reducing depressive symptoms. They are also well tolerated among patients infected with human immunodeficiency virus (HIV) and are using highly active antiretroviral treatment. This study seeks to ascertain that taking omega-3 fish oil  supplement has a significant positive effect on depressive symptoms among HIV infected pregnant women. This is a double-blind, parallel randomized control trial using fish oil omega-3 supplements and soybean oil soft gels. This study will be conducted in Nairobi City Council’s Kayole II Sub-district hospital, Mathare Health Centre, Riruta Health Centre and Kariobangi North Health Centre. A minimum total of 200 participants will be enrolled to receive either fish oil omega-3 of 3.00 g/day (EPA=2.25g/day; DHA=0.75 g/day) or a placebo of soybean oil soft gel, both from Innovix Pharma Inc to take orally, one soft gel three times per day in the morning, mid-day and evening after meals.  Only HIV-seropositive pregnant women with known CD4 cell count of not more than 500 cells/µl and are in their second trimester of pregnancy will be screened for participation. Those who meet the inclusion criteria and have not used medication for blood thinning conditions, diabetes or antidepressants two weeks prior to the study, signed the consent form and scored 14 or more on the BDI-II depressive symptom scale are enrolled in the trial. This is an 8-weeks intervention with bi-weekly monitoring and data collection intervals at the beginning, half way during the trial and at the end of eight weeks. The primary outcome of the study is depressive symptom scores measured by Beck Depression Inventory Second Edition (BDI-II) Scale and the secondary outcome is omega-3 status determined from cheek cell samples collected through mouth rinse method. The research will contribute to the debate on use of omega-3 fish oil in nutritional support and management of depressive symptoms and related health complications in HIV infected pregnant women and other vulnerable populations, to improve their mental health, hence improve the quality of life.