Microalgal photosynthesis provides energy and carbon-containing precursors for the biosynthesis of storage carbohydrates such as starch, chrysolaminarin, lipids, and cell wall components. Under mild nitrogen deficiency (N−), some Nannochloropsis species accumulate lipid by augmenting cytosolic fatty acid biosynthesis with a temporary increase in laminarin. Accordingly, biosynthesis of the cellulose-rich cell wall should change in response to N− stress because this biosynthetic pathway begins with utilisation of the hexose phosphate pool supplied from photosynthesis. However, few studies have characterised microalgal cell wall metabolism, including oleaginous Nannochloropsis sp. microalgae subjected to nitrogen deficiency. Here, we investigated N-induced changes in cellulose biosynthesis in N. salina. We observed that N− induced cell wall thickening, concurrently increased the transcript levels of genes coding for UDPG pyrophosphorylase and cellulose synthases, and increased cellulose content. Nannochloropsis salina cells with thickened cell wall were more susceptible to mechanical stress such as bead-beating and sonication, implicating cellulose metabolism as a potential target for cost-effective microalgal cell disruption.