Background and objectives Asthma is a common chronic inflammatory disorder of the lung that can be exacerbated by environmental triggers during sandstorms. This study aimed to evaluate the usefulness of C-C chemokine ligand 5 (CCL5) chemokine and interleukin 5 (IL-5) cytokine and determine the total eosinophil count in blood and sputum for use as biomarkers in Saudi patients with chronic asthma who visited emergency departments during sandstorms. Methods The study included 42 Saudi patients with chronic asthma and 20 healthy controls. Plasma levels of CCL5, IL-5, and total immunoglobulin E (IgE) were measured using a specific enzyme-linked immunosorbent assay (ELISA). Total eosinophils in peripheral blood were counted using a hematology analyzer (CELL-DYN Ruby System; Abbott Diagnostics, Chicago, Illinois); in sputum, eosinophils stained with Giemsa were examined under a microscope, counted, and expressed as a percentage of the total cells. Results Total IgE levels were significantly higher in patients with asthma (mean 433 IU/ml, P = 0.0001) as compared to normal controls (139 IU/ml). There was no significant difference in the levels of CCL5 in patients with asthma (625 pg/ml) as compared to normal controls (663 pg/ml, P = 0. 57). No correlation was found between total IgE and CCL5 levels. IL-5 was not detected in patients with asthma or in controls. Moreover, the total counts of eosinophils in the blood did not increase in patients with asthma as compared to controls while eosinophils in sputum samples were increased in the former (mean =3.128%). Conclusion Plasma levels of CCL5 and IL-5 or eosinophil counts in the peripheral blood may not be useful diagnostic biomarkers to evaluate airway inflammation and monitor asthma severity. Conversely, the sputum eosinophil count may represent a useful diagnostic marker for assessing the magnitude of asthma exacerbation during sandstorms.