The present study aims to evaluate pulmonary function tests and acute phase proteins in foals with respiratory distress syndrome (RDS) compared to apparently healthy foals. A total of 26 foals of both sexes collected from different farms at Sharqia Governorate, Egypt, were used in the present study. Seven foals were clinically healthy defined as a control group; showed no current or previous respiratory illness, and had normal blood hematology and biochemistry parameters. Nineteen foals presented with signs of respiratory distress syndrome, including increased body temperature, pulse, and respiratory rate, cough either on stimulation (37%) or spontaneous (63%), on auscultation of the lung there was exaggerated vesicular sound (32%), wheezing (37%), pleuritic frictional sound (26%) and absence of lung sound (26%). Hemoglobin, total protein, and albumin were decreased significantly in RDS foals compared to healthy foals. While, a significant increase in packed cell volume, erythrocytes, leucocytes, platelets, and neutrophils percent in RDS foals compared to healthy foals was observed. The RDS foals showed a significant reduction in blood pH and partial pressure of oxygen, base excess, and a significant increase in partial pressure of carbon dioxide and bicarbonate compared to healthy foals. Acute phase proteins showed a significant increase of SAA, haptoglobin, fibrinogen, and procalcitonin in RDS foals compared to healthy control foals. It is concluded that assessing pulmonary function tests and APPs concentration may serve as effective and early diagnostic tools for identifying foals affected by RDS.