Sugar beet (Beta vulgaris L.) is one of the main sources of sucrose, providing nearly 30% of sugar production worldwide. The viability of the crop is threatened by the attack of pathogens that cause various diseases, resulting in severe yield losses. The oomycete Aphanomyces cochlioides is one of the most problematic pathogens, due to its worldwide distribution and the ability to induce infection at any stage of sugar beet lifecycle, causing seedling damping-off and chronic root rot. During the early stages of sugar beet cultivation the infection can be controlled by the application of chemical fungicides on seeds. However, no major control measures are available for the disease management on mature roots. The genetic basis of resistance is still unclear, therefore the identification of genes associated with sugar beet defense responses is an important step for sustainable disease control. In this study, we performed a transcriptome analysis of partially resistant and susceptible sugar beet breeding lines infected with A. cochlioides. Differential expression analysis combined with Gene Ontology (GO) enrichment analysis revealed changes in genes associated to defense mechanisms during the early stages of infection. GO categories associated with hydrogen peroxide (H2O2) metabolism, detoxification and cell wall organization were significantly enriched in the differentially expressed gene set from the two partially resistant lines. The findings of this study shed light on the biological processes activated in response to A. cochlioides and can be used to assist sugar beet breeding in developing resistant varieties.