Both in Indonesia and Vietnam, larval rearing of Pangasius hypophthalmus remains problematic due to the variable and generally low survival rates obtained. The first week represents the most critical period for these larvae and up to now, cannibalistic behaviour was considered as the main cause of mortality. In the present study, two experiments were carried out in order to better understand the evolution and causes of mortality of P. hypophthalmus larvae from hatching up to 8 d of age and to find measures to improve survival rates. The first experiment was designed to evaluate the importance of cannibalism and differences in mortality when larvae from two different females were reared either in groups of 30 individuals or in isolated condition (30 larvae reared separately). In both cases, the culture was carried out either with or without antibiotic. The aim of the second experiment was to test oxytetracycline and different disinfectants (chloramine-T, formalin and ‘formalin + malachite green oxalate’) at different dosages in order to prevent bacterial outbreaks in the culture. The results indicated that the survival rates of P. hypophthalmus larvae was dependent on the initial quality of larvae or eggs and that larval mortality was more a consequence of pathogenic infection than a direct effect of cannibalism. The present study demonstrated that the survival rates of larvae were systematically improved when rearing was carried out in water containing antibiotic (oxytetracycline at a dose of 5 to 20 mg·L−1). Survival rate and final mean body weight of larvae as high as those obtained using antibiotic were also reached with applications of disinfectants such as chloramine-T and formalin. The use of these disinfectants is recommended for commercial P. hypophthalmus hatcheries.