Aim <p>Maxillofacial space infections (MSIs) are influenced by various systemic conditions; however, the impact of anaemia on infection severity and clinical outcomes remains underexplored. This prospective clinical study aimed to evaluate the role of pre-operative anaemia as a risk factor for the severity and progression of MSIs and its effect on clinical outcomes.</p> Methodology <p>A prospective cohort study was conducted on 181 patients diagnosed with MSIs. Data on demographics, haemoglobin levels, RBC counts, total WBC counts, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), random blood sugar (RBS), symptom severity score (SSS), length of hospital stay (LOHS), and antibiotic resistance patterns were collected and analysed.</p> Results <p>Significant differences were observed across anaemia grades in haemoglobin, RBC counts, CRP, NLR, and WBC counts. Lower haemoglobin levels were associated with higher SSS, prolonged hospital stay, and increased inflammatory markers. Moderate to severe anaemia demonstrated a stronger association with elevated CRP and NLR. A significant inverse relationship was observed between haemoglobin levels, inflammatory and clinical severity parameters. Total WBC count showed a weaker and less consistent association, with a declining trend in more severe anaemia.</p> Conclusion <p>Anaemia is an important factor associated with increased disease severity and adverse clinical outcomes in MSIs. NLR and CRP appear to be more reliable indicators of disease severity than total WBC count in anaemic patients.</p> Clinical trial number <p>Not applicable.</p>