Oliver Wendell Holmes Sr. is portrayed in a full seated cabinet card by Warren's studio, Boston, showing the physician, poet, and essayist in his later years in a relaxed and scholarly composition. Holmes sits in a tufted upholstered armchair, his body turned slightly to his left, holding an open book in his lap with both hands, while papers and additional books are arranged on a writing desk behind him with a decorative lamp visible at the rear. He wears a dark double-breasted frock coat and waistcoat over a white shirt with a dark cravat, his white hair neatly combed back, and a close-cropped white fringe at his jaw. His expression is calm and alert, his gaze directed toward the camera. The Warren's studio imprint appears in the characteristic red script on the front mount below the image.

The book in hand and writing materials behind constitute a deliberate scholarly setting befitting Holmes's dual identity as Harvard professor of anatomy and celebrated man of letters. The reverse bears the Warren's Portraits imprint at 465 Washington Street, Boston, in the same flowing red script as the front, with a bold flowing ink inscription reading Oliver Wendell Holmes at the top.

Oliver Wendell Holmes Sr. (1809–1894) was one of the most beloved figures in American letters and medicine, a professor of anatomy at Harvard Medical School for over thirty years and a founding contributor to The Atlantic Monthly, for which he wrote the enormously popular Autocrat of the Breakfast-Table series beginning in 1857. His poems Old Ironsides, The Chambered Nautilus, and The Last Leaf secured his place in American poetry, and his medical essay on the contagiousness of puerperal fever was a foundational contribution to American medical science.

The reverse bears an inscription reading Oliver Wendell Holmes in flowing ink script, the Warren's Portraits imprint at 465 Washington Street, Boston, and dealer code 7/21/12 / LOBCFZ / Eb.