Background: Acute streptococcal tonsillitis is a common upper respiratory tract infection that may be complicated by peritonsillar abscess (PTA), a condition associated with increased morbidity and the need for urgent intervention. Early differentiation between uncomplicated tonsillitis and PTA remains clinically challenging and reliance on imaging may be limited by availability, cost and radiation exposure. Therefore, readily available blood-based biomarkers may assist in early risk stratification. Objective: This study aimed to evaluate mean platelet volume (MPV), systemic immune-inflammation index (SII) and plateletcrit (PCT) as potential biomarkers for distinguishing uncomplicated streptococcal acute tonsillitis from tonsillitis complicated by peritonsillar abscess. Methods: This hospital-based case-control study was conducted at Imam Ali Hospital and Al-Kindy Teaching Hospital, Baghdad, Iraq, between February and December 2025. A total of 120 participants were enrolled, including 60 patients with streptococcal acute tonsillitis (with or without PTA) and 60 age- and sex-matched healthy controls. Complete blood count parameters were obtained at presentation. MPV was directly measured, while SII and PCT were calculated using standard formulas. Statistical comparisons, receiver operating characteristic (ROC) curve analysis and multivariate logistic regression were performed to assess diagnostic performance and predictive value. Results: MPV was significantly lower, while SII and PCT were significantly higher in cases compared with controls (p <0.01 for all). Among patients, those with PTA demonstrated significantly lower MPV and higher SII and PCT than those with uncomplicated tonsillitis. ROC analysis showed moderate diagnostic accuracy for MPV (AUC = 0.66), SII (AUC = 0.69) and PCT (AUC = 0.67) in predicting PTA. Multivariate analysis identified low MPV, elevated SII and elevated PCT as independent predictors of PTA. Conclusion: MPV, SII and PCT are inexpensive, readily available biomarkers that reflect inflammatory burden and platelet dynamics in streptococcal tonsillitis. Their combined assessment may aid early identification of patients at increased risk of peritonsillar abscess and support timely clinical decision-making, potentially reducing unnecessary imaging and delays in management.