Hospital-acquired anemia (HAA) is prevalent in patients hospitalized in the intensive care unit (ICU). Iatrogenic blood loss (IBL) may aggravate existing anemia or lead to a need for red blood cell (RBC) transfusion. The aim of our study was to analyze hemoglobin (Hb) concentration changes in up to 14 days, as well as all potential sources of IBL, in consecutive patients admitted to the intensive care unit (ICU) in the years 2020–2021. Patients admitted due to bleeding were excluded. Anemia on admission was present in 218 (58.8%) patients—47 (48.9%) surgical and 171 (62.2%) non-surgical (p = 0.02). Gradual decrease in Hb was seen in all ICU patients. Eighty-one (21.8%) patients required RBC transfusion. The first unit of RBC was transfused on day 7 (IQR 2–13) and the second on day 11 (IQR 4–15) of ICU hospitalization. The median admission Hb in patients who required RBC transfusion was 10.2 (IQR 8.5–11.8) and, in those who did not require transfusion, it was 12.0 (IQR 10.2–13.6) g/dL (p < 0.01). Anemia on admission was associated with a need for RBC transfusion (p < 0.01). Average decrease in Hb during the first week of ICU hospitalization in patients with and without anemia on admission was 1.2 (IQR 0.2–2.3) and 2.8 (IQR 1.1–3.8) g/dL (p < 0.01), respectively. Percentage of patients who bled at the insertion site of invasive devices was as follows: percutaneous tracheostomy—46.7%, therapeutic plasma exchange (TPE) catheter—23.8%, dialysis catheter—13.3%, gastrostomy—9.5%, central venous catheter—7.8%. Moreover, circuit clotting occurred in 17.7 and 9.5% of patients undergoing dialysis and TPE, respectively. Median blood loss for repeated laboratory testing in our study population was 13.7 (IQR 9.9–19.3) mL per patient daily. Anemia is highly prevalent among medical and surgical patients on admission to ICU and is associated with RBC transfusion. Patients who required RBC transfusion had significantly lower daily Hb concentrations. Severity of disease did not seem to have impact on Hb concentration. IBL associated with invasive devices and extracorporeal therapies is frequent in ICU patients and may lead to a gradual decrease in Hb concentration. Further studies are required to analyze causes of HAA in the ICU.