The current study was conducted on multiple oral doses (40 mg/kg for 3 successive days) of florfenicol (FF) to determine its effect on some hematological parameters, cardiac enzymes and its residues in blood and tissues (liver, muscles and kidneys) of broiler chickens. Seventy broiler chickens were used and divided into two groups, each consisted of 35 birds. The first group was left as a control, while the second was given FF for 3 successive days. The FF residues in tissues were determined using reversed phase-high performance liquid chromatography (RP-HPLC) with ultraviolet (UV) detector at 223 nm. Results indicated a widespread distribution of FF in most of the tested tissues. All tissue samples were considered FF free on the 9th day after the last oral dose except liver. Florfenicol administration elicited a significant decrease in all blood parameters (hemoglobin concentration (Hb), red blood cell count (RBCs), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) and lymphocytes) from 1st up to 7th day except packed cell volume (PCV) which showed no significant change on 1st day but decreased on 3rd, 5th and 7th day after stopping medication. Moreover, monocytopenia was observed on the 5th and 7th day and white blood cells (WBCs) showed the same effect on the 5th day, while heterophiles revealed highly elevation. All cardiac enzymes (aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB) and Troponin I) were highly elevated. In conclusion, broiler chicken meat can be consumed safely after 9 days post FF treatment.