Oreochromis karongae is one of the three key Tilapia species locally known as 'Chambo' which is endemic to Lake Malawi. The species is favored by consumers and due to high demand its catches have significantly declined over time. Aquaculture holds the potential to supplement catches as well as produce seed for restocking purposes. However, seed production of O.karongae in artificial hatcheries has registered little success due to high egg and fry mortalities. Therefore, a study was conducted to compare the apparent effectiveness of three chemical egg disinfectants in an attempt to improve hatching success and reduce fry mortality in O. karongae in an artificial re-circulating incubation system at the National Aquaculture Center, Domasi, Malawi. Batches of 200 stage II eggs were immersed for 5 minutes in 50ml solutions of (1) 50mg/l Potassium Permanganate, (2) 500mg/l Formalin, (3) 1000mg/l Sodium Chloride, (4) 5000mg/l Sodium Chloride, while treatment (5) was a control without any chemical treatment. Each treatment was replicated three times in 1.2 L plastic incubation jars with continuous water flow rate of 0.17 l/s operated at 10% daily water replacement. There was significantly low total mortality and high hatchability in treatments (1), (2) and (3) than (4) and (5) (p<0.05). The results provided evidence that pre-incubation egg treatment using chemicals has potential to significantly reduce mortalities and increase fry production in an artificial re-circulating incubation system. It is recommended, based on the findings that lower concentrations of sodium chloride, being a safer and less toxic chemical can be used for disinfecting O.karongae eggs. Future studies should focus on undertaking a toxicity test with various levels of the chemical disinfectants to identify optimum doses. This should be coupled with microbiological assays to validate the apparent effectiveness found in this study and identify the key microbial species that are responsible for mortalities during incubation of O.karongae eggs in a re-circulating system.