Anemia is common in critically ill patients; almost 95% of patients admitted to intensive care units (ICUs) have hemoglobin levels below normal. Several causes may explain this phenomenon as well as the tendency to transfuse patients without adequate cause: due to a lack of adherence to protocols, lack of supervision, incomplete transfusion request forms, or a lack of knowledge about the indications, risks, and costs of transfusions. Daily sampling to monitor the coagulation parameters and the acid-base balance can aggravate anemia as the main iatrogenic factor in its production. We studied the association and importance of iatrogenic blood loss and other factors in the incidence of anemia in ICUs. We performed a prospective, observational, multicenter study in five Spanish hospitals. A total of 142 patients with a median age of 58 years (IQI: 48-69), 71.83% male and 28.17% female, were admitted to ICUs without a diagnosis of iatrogenic anemia. During their ICU stay, anemia appeared in 66.90% of the sample, 95 patients, (95% CI: 58.51-74.56%). Risk factors associated with the occurrence of iatrogenic anemia were arterial catheter insertion (72.63% vs. 46.81%, -value = 0.003), venous catheter insertion (87.37% vs. 72.34%, -value = 0.023), drainages (33.68% vs. 12. 77%, -value = 0.038), and ICU stay, where the longer the stay, the higher the rate of iatrogenic anemia (-value < 0.001). We concluded that there was a statistical significance in the production of iatrogenic anemia due to the daily sampling for laboratory monitoring and critical procedures in intensive care units. The implementation of patient blood management programs could address these issues.