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Objectives Cognitive symptoms or ‘brain fog’ are common in systemic lupus erythematosus (SLE) and may reflect cognitive fatigue (CF) rather than measurable impairment. Neuroimaging indicates compensatory mechanisms that sustain performance but increase effort and fatigue. Eye-tracking provides an objective index of CF via pupil dilation, a marker of cognitive effort. We evaluated whether pupil-based eye-tracking detects CF in SLE and whether cognitive effort differs between SLE and healthy-controls (HC).Methods SLE participants fulfilling EULAR/ACR criteria and HCs were recruited. This study is part of a larger task-based fMRI project investigating altered brain mechanisms in SLE. During scanning, participants completed a two-staged cognitive task assessing working memory (WM) and long-term memory retrieval while eye-tracking data were recorded at 60 Hz. Baseline-corrected pupil timeseries and average diameter were calculated per trial, artefacts and blinks were removed, and participants with <40% valid data were excluded. Stage 1 examined encoding, WM, and confirmation of retained information (stimulus, gap, position) across three 45-trial blocks. Stage 2 assessed retrieval of Stage-1 stimuli ( figure 1). For Stage 1, pupil timeseries were analysed with a mixed-design ANOVA with Phase, Block, and Time (10 bins) as within-subjects factors and Group (SLE, HC) as the between-subjects factor. For Stage 2, memory accuracy was compared between groups, and average pupil responses were analysed with a mixed ANOVA with accuracy (accurate, inaccurate) and group (SLE, HC).Results Data from 40 SLE patients and 18 HCs were collected ( table 1). After quality control, pupillometry analyses included 19 SLE and 8 HCs. In Stage 1, we observed significant effects of Phase (p=0.014) and Time (p=0 .001), and a Phase×Time×Group interaction (p=0.048). SLE participants showed greater pupil dilation during the position phase, indicating increased cognitive effort and fatigue. In Stage 2, no significant effects of accuracy, group, or their interaction were detected (all p>0.35), indicating comparable retrieval-related effort (figure 2).Abstract PO:09:249 Table 1Participant characteristicsAbstract PO:09:249 Figure 1–2Conclusions SLE participants displayed distinct pupil dynamics during WM engagement, consistent with increased cognitive effort and potential compensatory mechanisms. No group differences emerged during retrieval. Pupillometry provides a sensitive, non-invasive biomarker of CF in SLE and a complement to imaging as a potential objective measure of patient-reported ‘brain fog’.