The delayed non-match to position task (DNMTP) is a translational instrumental learning paradigm commonly applied preclinically to assess higher executive functions including attention and working memory in rats. In this study, the effects of acute inflammatory challenges were assessed on cognitive performance in the DNMTP task.. Male and female Wistar rats were trained to criteria on the task. Initially, in validating the test, the effect of treatment with the muscarinic receptor antagonist scopolamine (0.02mg/kg, s.c.), known to disrupt performance in the task, was confirmed. Sex differences emerged between males and females’ mnemonic response to lipopolysaccharide (LPS, 0.25mg/kg, i.p.) 24-hours post-administration with females showing cognitive impairment at higher working memory loads compared to males. Co-administration of cognitive enhancing agents including the acetylcholinesterase inhibitor donepezil (0.3mg/kg, s.c.) or long-acting β2-adrenergic agonist formoterol (0.5mg/kg s.c.) attenuated LPS-driven mnemonic impairments in males only. Paraventricular brain regions like the locus coeruleus (LC), a noradrenergic hub, are selectively vulnerable to systemic inflammation. The effect of direct stereotactic delivery of LPS (5μg/μl) to the LC was investigated to further assess cognitive performance in the DNMTP task. Despite LPS-induced microglial activation and noradrenergic neuronal cell loss in the LC, no deficit to pre-conditioned DNMTP performance was observed. Decrements however to spontaneous alternation behaviour were observed on a Y-maze paradigm following intra-LC LPS delivery, indicative of a short-term spatial working memory impairment. Overall, the results show DNMTP as a test sensitive to acute systemic inflammation and indicates formoterol as a useful pro-cognitive anti-inflammatory agent in mitigating inflammatory-induced cognitive impairment.