The presence of alpha thalassemia and levels of hemoglobin F (HbF) significantly influence the clinical presentation of sickle cell disease (SCD) across different populations. This study was conducted to investigate the effects of these two factors on SCD patients in northern Iraq. A total of 74 patients with sickle/β0 thalassemia or sickle cell anemia, with a mean age of 16 years, participated in the study, of which 56.8% were male. Comprehensive clinical evaluations and lab tests were performed, including blood and reticulocyte counts, HbF levels, and analysis of serum lactic dehydrogenase and bilirubin. Screening for alpha-thalassemia mutations was performed using multiplex PCR and reverse hybridization. The results showed a positive correlation between HbF levels and hemoglobin, as well as negative correlations with reticulocyte count, HbA2, and the frequency of blood transfusions (P = 0.033, 0.041, 0.037, and 0.02, respectively). However, HbF was not correlated with other clinical symptoms. Nine patients had alpha-thalassemia (eight with –α3.7/αα and one with –α4.2/αα), but no significant hematological or clinical effects were observed in these patients. This study showed that HbF, rather than alpha-thalassemia, primarily modulates the disease phenotype in SCD patients from northern Iraq, which is different from findings in populations from Africa, the Arabian Peninsula, and Iraq, where alpha-thalassemia often plays a more influential role, sometimes more than HbF.