Schizochytrium mangrovei strain PQ6 was investigated for coproduction of docosahexaenoic acid (C22: 6ω-3, DHA) and squalene using a 30-L bioreactor with a working volume of 15 L under various batch and fed-batch fermentation process regimes. The fed-batch process was a more efficient cultivation strategy for achieving higher biomass production rich in DHA and squalene. The final biomass, total lipid, unsaponifiable lipid content, and DHA productivity were 105.25 g · L , 43.40% of dry cell weight, 8.58% total lipid, and 61.66 mg · g · L , respectively, after a 96 h fed-batch fermentation. The squalene content was highest at 48 h after feeding glucose (98.07 mg · g of lipid). Differences in lipid accumulation during fermentation were correlated with changes in ultrastructure using transmission electron microscopy and Nile Red staining of cells. The results may be of relevance to industrial-scale coproduction of DHA and squalene in heterotrophic marine microalgae such as Schizochytrium.