Aims: Platelet counts could possibly be used as prognostic markers in SCD, since they play an important role in the phenomena of vessel occlusion. In this context, the mean platelet volume (MPV) may also reflect the level of platelet activation. The aim of this study was to evaluate platelet counts and MPV as possible prognostic markers for the occurrence of sickle complications and their relationship with markers of inflammation and hemolysis. Methods: A retrospective chart review was performed on 266 SCD patients (median age 40 years, 14-66), followed from 2002 to 2019, distributed as: 156 HbSS, 16 HbSβ0, 15 HbSβ+ and 79 HbSC. Medical records were reviewed for laboratory data at baseline; clinical data and hospital admissions were recorded for SCD related complications throughout follow-up. Results: The median platelet count was significantly different between the different genotypes (Kruskal-Wallis rank sum test, p<0.001): SS, 420 (95-1043) x 103/uL; Sβ0, 406 (206-713); Sβ+, 362 (87-925); and SC, 295 (84-927). Regardless of the genotypes, platelet counts tend to decrease with age (Rô=-0.201, p<0.001). Higher platelet counts are associated with the presence of leg ulcers (Wilcoxon rank sum test with continuity correction, p=0.03), acute chest syndrome (p=0.04), higher levels of microalbuminuria (p<0.001) and transfusion load throughout life (p=0.03), pointing to a marker of disease severity. In addition, patients with higher platelet counts tend to have lower hemoglobin (Rô=-0.252, p<0.001) and hematocrit levels (Rô=-0.229, p<0.001), as well as higher RDW (Rô=0.131, p=0.032), probably related to the presence of immature forms in peripheral blood and representing higher levels of hemolysis, which is also corroborated by higher reticulocyte counts (Rô=0.333, p<0.001) and indirect bilirubin (Rô=0.227, p<0.001). There was also a positive relationship between platelet counts and number of total leukocytes (Rô=0.343, p<0.001), neutrophils (Rô=0.272, p<0.001), monocytes (Rô=0.28, p<0.001) and lymphocytes (Rô=0.257, p<0.001), probably reflecting an state of exacerbated inflammation. Rare patients (3.75%) have elevated MPV, but MPV seems to predict the occurrence of retinopathy in HbSC individuals (Wilcoxon rank sum test with continuity correction, p=0.05) and there is an inverse relationship between MPV and hemoglobin (Rô=-0.125, p=0.041) and hematocrit (Rô=-0.156, p=0.011). Discussion: In this cohort of Brazilian patients, the increase in platelet counts is related to a greater chance of leg ulcers, Acute Chest Syndrome, microalbuminuria and high transfusion load. Furthermore, they correlate inversely with hemoglobin and hematocrit levels, and are associated with changes in hemolysis and inflammation markers. MPV is related to the presence of retinopathy in HbSC individuals and MPV elevation is also associated with low levels of hemoglobin and hematocrit. Conclusion: It is important to evaluate the baseline platelet counts of SCD patients as possible predictors of clinical complications and more severe phenotypes. This simple measure has the potential to raise awareness in the care of these patients and to direct greater efforts in the prevention of chronic complications, especially in situations of less resources, as this is a cheap and easily available marker.