Campylobacter jejuni is one of the major bacterial causes of foodborne gastroenteritis worldwide. Despite this health burden, how C. jejuni interacts with the intrinsic defence mechanisms of intestinal epithelial cells (IECs) remains elusive. To address this, an initial investigation into how C. jejuni counteracts reactive oxygen species (ROS) was undertaken. C. jejuni was shown to differentially regulate ROS production in T84 and Caco-2 IECs. C. jejuni downregulated NAPDH oxidase (NOX1), a key ROS-generating enzyme in IECs. Furthermore, inhibition of NOX1 by either diphenyleneiodonium chloride (DPI) or siRNA transfection reduced C. jejuni pathogenesis within IECs. Both DPI treatment and siRNA transfection resulted in reduced fibronectin, a glycoprotein in extracellular matrix. These findings provide mechanistic insight into how C. jejuni modulates the ROS-related host defence mechanisms. A further investigation was performed into the potential mechanism of C. jejuni-mediated inflammation. Intestinal inflammation is associated with the unfolded protein response (UPR), a pathway involved in ER homeostasis. C. jejuni was shown to activate the PERK, IRE1α and ATF6 pathways in IECs in a strain- and cell line-dependent manner. Capsular polysaccharide, flagella and FlpA adhesin were shown to have a role during PERK pathway activation. The impact of the UPR on C. jejuni pathogenesis in IECs was also investigated. Pre-treatment with thapsigargin reduced C. jejuni intracellular survival whilst pre-treatment with UPR inhibitors increased intracellular C. jejuni numbers in IECs. The relationship between the UPR and inflammation was further investigated. C. jejuni-mediated interleukin-8 (IL-8) secretion was decreased with pre-treatment with the PERK inhibitor GSK2656157 and the IRE1α kinase/RNase inhibitor KIRA6. In contrast, pre-treatment with the IRE1α RNase inhibitor STF-083010 increased C. jejuni-mediated IL-8 secretion. In addition, C. jejuni-mediated UPR activation was independent of the increase in intracellular free calcium. These findings will form the basis for understanding the mechanisms of C. jejuni-induced UPR and UPR-mediated inflammation. Collectively, this study investigating C. jejuni-induced NOX1 modulation and UPR activation in human IECs provides exploration of survival mechanisms of C. jejuni within human IECs and pathogenic mechanisms which may lead to C. jejuni-induced inflammatory diarrhoea.