Background: The aetiology of postdialysis fatigue (PDF), an intermittent but debilitating fatigue occurring after haemodialysis (HD) treatment, is still unclear. In other inflammatory diseases, increasing evidence points toward the involvement of the immune system in the onset of fatigue symptoms. Altered serum levels of inflammatory cytokines have also been shown in HD patients. Therefore, we investigated whether pre- and postdialysis serum levels of pro- and anti-inflammatory cytokines (i.e. IL-1β, IL-6, TNF-α and IL-10) or their intradialytic changes (if any) were related to PDF or the time HD patients reported needing to recover from HD treatment (TIRD). Methods: Serum levels of IL-1β, IL-6, TNF-α and IL-10 were measured immediately before and after HD in 45 patients using commercially available kits on an ELLA™ automated immunoassay system. The presence and severity of PDF as well as TIRD duration were assessed by self-report measures. Key results: Seventy-four percent of patients reported PDF, with a median PDF severity index of 3.30 [IQR: 3.00–4.30] on a scale from 1 to 5. Median TIRD was 120 min [IQR: 60–480]. PDF severity correlated strongly with TIRD, rs = 0.85, p < 0.001. Only predialysis levels of IL-10 significantly and positively correlated with PDF severity (rs = 0.43, p = 0.003). Conclusion: Findings of the present study do not support the involvement of the immune system in the onset of PDF or the time patients needed to recover from HD treatment. A positive, but counterintuitive relationship was found between predialysis levels of anti-inflammatory IL-10 and PDF severity, which warrants further research.