。
She spoke in a quiet voice.
Literal
She [topic-は] quiet voice [with-で] spoke.
小さい声で uses the instrumental で to mark the manner of speaking. Japanese commonly builds this pattern with [adjective + 声 + で] to describe how someone speaks: 大きい声で (in a loud voice), 優しい声で (in a gentle voice), 怒った声で (in an angry voice). The related compound noun 小声 (こごえ) packs the same idea into a single word with a slightly more specific nuance of deliberately keeping one's voice down.