In this paper, we investigated the cultivation of Chlorella sp. in media containing low concentration of Ca and Mg. We assessed differences in biomass and lipid productivities relative to cultures grown in standard media that typically have 8X higher concentration of Ca and 30x higher concentration of Mg. Both N- sufficient and N-deficient standard media were used in this study as controls. In addition to growth (cell number and cell dry weight), we assessed N-utilization and accumulation of storage products (lipid and starch). We also monitored change in cell size and photosynthetic activity. The results showed that cell size, cell replication and N consumption rate were highest for cultures with low Ca possibly due to decreased cell wall rigidity and improved nutrient permeability through cell membrane. The results indicated that low Ca and Mg cultures had 50% higher starch concentration and nearly 4 fold higher lipid concentration (measured as fatty acid methyl ester) than standard media controls (with standard concentration of Ca, Mg and N). Our data suggests that the lipid accumulation of cells cultivated in low Ca or low Mg media occurs from de novo synthesis of these carbon/energy storage molecules. On the other hand, the majority of lipid accumulation for N deficient cultures likely originates from the interconversion of the protein and starch within the cells to lipid during N-starvation. Overall, our results suggest that cultivation of microalgae in low Ca media followed by N-starvation is likely to result in higher final biomass and lipid productivity.